Metastatic brain tumors: from development to cutting-edge treatment

Abstract

Metastatic brain tumors, also called brain metastasis (BM), represent a challenging complication of advanced tumors. Tumors that commonly metastasize to the brain include lung cancer and breast cancer. In recent years, the prognosis for BM patients has improved, and significant advancements have been made in both clinical and preclinical research. This review focuses on BM originating from lung cancer and breast cancer. We briefly overview the history and epidemiology of BM, as well as the current diagnostic and treatment paradigms. Additionally, we summarize multiomics evidence on the mechanisms of tumor occurrence and development in the era of artificial intelligence and discuss the role of the tumor microenvironment. Preclinically, we introduce the establishment of BM models, detailed molecular mechanisms, and cutting-edge treatment methods. BM is primarily treated with a comprehensive approach, including local treatments such as surgery and radiotherapy. For lung cancer, targeted therapy and immunotherapy have shown efficacy, while in breast cancer, monoclonal antibodies, tyrosine kinase inhibitors, and antibody–drug conjugates are effective in BM. Multiomics approaches assist in clinical diagnosis and treatment, revealing the complex mechanisms of BM. Moreover, preclinical agents often need to cross the blood–brain barrier to achieve high intracranial concentrations, including small-molecule inhibitors, nanoparticles, and peptide drugs. Addressing BM is imperative.

Keywords

diagnosis and treatment / metastatic brain tumors / molecular mechanisms / multiomics / tumor microenvironment

References

[1] Boire A, Brastianos PK, Garzia L, Valiente M. Brain metastasis. Nat Rev Cancer. 2020; 20(1): 4-11.

[2] Miccio JA, Tian Z, Mahase SS, et al. Estimating the risk of brain metastasis for patients newly diagnosed with cancer. Commun Med (Lond). 2024; 4(1): 27.

[3] Relli V, Trerotola M, Guerra E, Alberti S. Abandoning the notion of non-small cell lung cancer. Trends Mol Med. 2019; 25(7): 585-594.

[4] Gillespie CS, Mustafa MA, Richardson GE, et al. Genomic alterations and the incidence of brain metastases in advanced and metastatic NSCLC: a systematic review and meta-analysis. J Thorac Oncol. 2023; 18(12): 1703-1713.

[5] Scandurra G, Lombardo V, Scibilia G, et al. New frontiers in the treatment of patients with HER2+ cancer and brain metastases: is radiotherapy always useful? Cancers (Basel). 2024; 16(13): 2466.

[6] Poletes C, Amanirad B, Santiago AT, et al. The incidence of brain metastases in breast cancer according to molecular subtype and stage: a 10-year single institution analysis. J Neurooncol. 2024; 169(1): 119-127.

[7] Ge H, Zhu K, Sun Q, et al. The clinical, molecular, and therapeutic implications of time from primary diagnosis to brain metastasis in lung and breast cancer patients. Cancer Med. 2024; 13(11): e7364.

[8] Kuksis M, Gao Y, Tran W, et al. The incidence of brain metastases among patients with metastatic breast cancer: a systematic review and meta-analysis. Neuro Oncol. 2021; 23(6): 894-904.

[9] He Y, Shao Y, Chen Q, Liu C, Zhu F, Liu H. Brain metastasis in de novo stage IV breast cancer. Breast. 2023; 71: 54-59.

[10] Jiang K, Parker M, Materi J, et al. Epidemiology and survival outcomes of synchronous and metachronous brain metastases: a retrospective population-based study. Neurosurg Focus. 2023; 55(2): E3.

[11] Wang C, Xiang J, Zhang Q, Li J, Liu Y, Liu J. Intracranial efficacy of pyrotinib and capecitabine combination therapy in HER2-positive breast cancer with brain metastases. Drug Des Devel Ther. 2024; 18: 909-917.

[12] Guomundsson KR. A survey of tumors of the central nervous system in Iceland during the 10-year period 1954–1963. Acta Neurol Scand. 1970; 46(4): 538-552.

[13] Percy AK, Elveback LR, Okazaki H, Kurland LT. Neoplasms of the central nervous system. Epidemiologic considerations. Neurology. 1972; 22(1): 40-48.

[14] Fogelholm R, Uutela T, Murros K. Epidemiology of central nervous system neoplasms. A regional survey in Central Finland. Acta Neurol Scand. 1984; 69(3): 129-136.

[15] Sul J, Posner JB. Brain metastases: epidemiology and pathophysiology. Cancer Treat Res. 2007; 136: 1-21.

[16] Posner JB, Chernik NL. Intracranial metastases from systemic cancer. Adv Neurol. 1978; 19: 579-592.

[17] Lokich JJ. The management of cerebral metastasis. JAMA. 1975; 234(7): 748-751.

[18] Gawler J, Bull JW, Du Boulay GH, Marshall J. Computer-assisted tomography (EMI scanner). Its place in investigation of suspected intracranial tumours. Lancet. 1974; 2(7878): 419-423.

[19] Lin JP, Kricheff, II, Laguna J, Naidich T. Brain tumors studied by computerized tomography. Adv Neurol. 1976; 15: 175-199.

[20] Graif M, Bydder GM, Steiner RE, Niendorf P, Thomas DG, Young IR. Contrast-enhanced MR imaging of malignant brain tumors. AJNR Am J Neuroradiol. 1985; 6(6): 855-862.

[21] Suh CH, Jung SC, Kim KW, Pyo J. The detectability of brain metastases using contrast-enhanced spin-echo or gradient-echo images: a systematic review and meta-analysis. J Neurooncol. 2016; 129(2): 363-371.

[22] Larkin JR, Simard MA, de Bernardi A, Johanssen VA, Perez-Balderas F, Sibson NR. Improving delineation of true tumor volume with multimodal MRI in a rat model of brain metastasis. Int J Radiat Oncol Biol Phys. 2020; 106(5): 1028-1038.

[23] Wong TZ, van der Westhuizen GJ, Coleman RE. Positron emission tomography imaging of brain tumors. Neuroimaging Clin N Am. 2002; 12(4): 615-626.

[24] Jones T, Rabiner EA, Company PETRA. The development, past achievements, and future directions of brain PET. J Cereb Blood Flow Metab. 2012; 32(7): 1426-1454.

[25] Brooks WH, Mortara RH, Preston D. The clinical limitations of brain scanning in metastatic disease. J Nucl Med. 1974; 15(7): 620-621.

[26] Rohren EM, Provenzale JM, Barboriak DP, Coleman RE. Screening for cerebral metastases with FDG PET in patients undergoing whole-body staging of non-central nervous system malignancy. Radiology. 2003; 226(1): 181-187.

[27] Cicone F, Minniti G, Romano A, et al. Accuracy of F-DOPA PET and perfusion-MRI for differentiating radionecrotic from progressive brain metastases after radiosurgery. Eur J Nucl Med Mol Imaging. 2015; 42(1): 103-111.

[28] Tomura N, Kokubun M, Saginoya T, Mizuno Y, Kikuchi Y. Differentiation between treatment-induced necrosis and recurrent tumors in patients with metastatic brain tumors: comparison among (11)C-methionine-PET, FDG-PET, MR permeability imaging, and MRI-ADC-preliminary results. AJNR Am J Neuroradiol. 2017; 38(8): 1520-1527.

[29] Rybarczyk-Kasiuchnicz A, Ramlau R, Stencel K. Treatment of brain metastases of non-small cell lung carcinoma. Int J Mol Sci. 2021; 22(2): 593.

[30] Wang Z, Wang Y, Chang M, et al. Single-cell transcriptomic analyses provide insights into the cellular origins and drivers of brain metastasis from lung adenocarcinoma. Neuro Oncol. 2023; 25(7): 1262-1274.

[31] Xiao G, Li L, Tanzhu G, et al. Heterogeneity of tumor immune microenvironment of EGFR/ALK-positive tumors versus EGFR/ALK-negative tumors in resected brain metastases from lung adenocarcinoma. J Immunother Cancer. 2023; 11(3): e006243.

[32] Zhang Q, Abdo R, Iosef C, et al. The spatial transcriptomic landscape of non-small cell lung cancer brain metastasis. Nat Commun. 2022; 13(1): 5983.

[33] Achrol AS, Rennert RC, Anders C, et al. Brain metastases. Nat Rev Dis Primers. 2019; 5(1): 5.

[34] Zhu Y, Cui Y, Zheng X, Zhao Y, Sun G. Small-cell lung cancer brain metastasis: from molecular mechanisms to diagnosis and treatment. Biochim Biophys Acta Mol Basis Dis. 2022; 1868(12): 166557.

[35] Osmani L, Askin F, Gabrielson E, Li QK. Current WHO guidelines and the critical role of immunohistochemical markers in the subclassification of non-small cell lung carcinoma (NSCLC): moving from targeted therapy to immunotherapy. Semin Cancer Biol. 2018; 52(Pt 1): 103-109.

[36] Nooreldeen R, Bach H. Current and future development in lung cancer diagnosis. Int J Mol Sci. 2021; 22(16): 8661.

[37] Ozcan G, Singh M, Vredenburgh JJ. Leptomeningeal metastasis from non-small cell lung cancer and current landscape of treatments. Clin Cancer Res. 2023; 29(1): 11-29.

[38] Tsakonas G, Tadigotla V, Chakrabortty SK, et al. Cerebrospinal fluid as a liquid biopsy for molecular characterization of brain metastasis in patients with non-small cell lung cancer. Lung Cancer. 2023; 182: 107292.

[39] Derks S, van der Veldt AAM, Smits M. Brain metastases: the role of clinical imaging. Br J Radiol. 2022; 95(1130): 20210944.

[40] Hendriks LE, Kerr KM, Menis J, et al. Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023; 34(4): 339-357.

[41] Hendriks LE, Kerr KM, Menis J, et al. Non-oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023; 34(4): 358-376.

[42] Cardinal T, Pangal D, Strickland BA, et al. Anatomical and topographical variations in the distribution of brain metastases based on primary cancer origin and molecular subtypes: a systematic review. Neurooncol Adv. 2022; 4(1): vdab170.

[43] Bonert M, Berzins A, Begum H, et al. Neuroanatomical location of brain metastases from solid tumours based on pathology: An analysis of 511 patients with a comparison to the provided clinical history. PLoS One. 2023; 18(11): e0294154.

[44] Mahmoodifar S, Pangal DJ, Neman J, et al. Comparative analysis of the spatial distribution of brain metastases across several primary cancers using machine learning and deep learning models. J Neurooncol. 2024; 167(3): 501-508.

[45] Shi W, Wang Y, Xia W, et al. Brain metastases from small cell lung cancer and non-small cell lung cancer: comparison of spatial distribution and identification of metastatic risk regions. J Neurooncol. 2023; 161(1): 97-105.

[46] Wang Y, Xia W, Liu B, et al. Exploration of spatial distribution of brain metastasis from small cell lung cancer and identification of metastatic risk level of brain regions: a multicenter, retrospective study. Cancer Imaging. 2021; 21(1): 41.

[47] Han YM, Ou D, Chai WM, et al. Exploration of anatomical distribution of brain metastasis from breast cancer at first diagnosis assisted by artificial intelligence. Heliyon. 2024; 10(9): e29350.

[48] Neman J, Franklin M, Madaj Z, et al. Use of predictive spatial modeling to reveal that primary cancers have distinct central nervous system topography patterns of brain metastasis. J Neurosurg. 2022; 136(1): 88-96.

[49] Teunissen WHT, Govaerts CW, Kramer MCA, et al. Diagnostic accuracy of MRI techniques for treatment response evaluation in patients with brain metastasis: A systematic review and meta-analysis. Radiother Oncol. 2022; 177: 121-133.

[50] Ozutemiz C, White M, Elvendahl W, et al. Use of a commercial 7-T MRI scanner for clinical brain imaging: indications, protocols, challenges, and solutions-a single-center experience. AJR Am J Roentgenol. 2023; 221(6): 788-804.

[51] Cheng K, Duan Q, Hu J, et al. Evaluation of postcontrast images of intracranial tumors at 7T and 3T MRI: An intra-individual comparison study. CNS Neurosci Ther. 2023; 29(2): 559-565.

[52] Berger A, Lee MD, Lotan E, Block KT, Fatterpekar G, Kondziolka D. Distinguishing brain metastasis progression from radiation effects after stereotactic radiosurgery using longitudinal GRASP dynamic contrast-enhanced MRI. Neurosurgery. 2023; 92(3): 497-506.

[53] Li Y, Lv X, Wang B, et al. Predicting EGFR T790M mutation in brain metastases using multisequence MRI-based radiomics signature. Acad Radiol. 2023; 30(9): 1887-1895.

[54] Liberini V, Pizzuto DA, Messerli M, et al. BSREM for brain metastasis detection with 18F-FDG-PET/CT in lung cancer patients. J Digit Imaging. 2022; 35(3): 581-593.

[55] Oen SK, Johannessen K, Pedersen LK, et al. Diagnostic value of 18 F-FACBC PET/MRI in brain metastases. Clin Nucl Med. 2022; 47(12): 1030-1039.

[56] Young JR, Ressler JA, Mortimer JE, Schmolze D, Fitzgibbons M, Chen BT. Association between (18)F-FDG PET activity and HER2 status in breast cancer brain metastases. Nucl Med Mol Imaging. 2024; 58(3): 113-119.

[57] Morganti S, Parsons HA, Lin NU, Grinshpun A. Liquid biopsy for brain metastases and leptomeningeal disease in patients with breast cancer. NPJ Breast Cancer. 2023; 9(1): 43.

[58] Nicolo E, Gianni C, Curigliano G, Reduzzi C, Cristofanilli M. Modeling the management of patients with human epidermal growth factor receptor 2-positive breast cancer with liquid biopsy: the future of precision medicine. Curr Opin Oncol. 2024; 36(6): 503-513.

[59] Chen K, Yang F, Shen H, et al. Individualized tumor-informed circulating tumor DNA analysis for postoperative monitoring of non-small cell lung cancer. Cancer Cell. 2023; 41(10): 1749-1762. e6.

[60] Mack PC, Miao J, Redman MW, et al. Circulating tumor DNA kinetics predict progression-free and overall survival in EGFR TKI-treated patients with EGFR-mutant NSCLC (SWOG S1403). Clin Cancer Res. 2022; 28(17): 3752-3760.

[61] Peng L, Bin Y, Ding P, et al. Integrated circulating tumor DNA and T cell repertoire predict radiotherapeutic response and outcome in non-small cell lung cancer patients with brain metastasis. Cancer Commun (Lond). 2023; 43(5): 625-629.

[62] Callesen LB, Boysen AK, Andersen RF, Dalby RB, Spindler KG. Circulating DNA and frequency of colorectal cancer brain metastases in a presumed high-risk group. Sci Rep. 2023; 13(1): 18574.

[63] Cheok SK, Narayan A, Arnal-Estape A, et al. Tumor DNA mutations from intraparenchymal brain metastases are detectable in CSF. JCO Precis Oncol. 2021; 5.

[64] Wu J, Liu Z, Huang T, et al. Cerebrospinal fluid circulating tumor DNA depicts profiling of brain metastasis in NSCLC. Mol Oncol. 2023; 17(5): 810-824.

[65] Qin X, Bai Y, Zhou S, et al. Early diagnosis of brain metastases using cerebrospinal fluid cell-free DNA-based breakpoint motif and mutational features in lung cancer. Clin Transl Med. 2023; 13(3): e1221.

[66] Qiao S, Hao Y, Cai L, et al. Prognostic value of cell-free DNA in cerebrospinal fluid from lung cancer patients with brain metastases during radiotherapy. Radiat Oncol. 2023; 18(1): 50.

[67] Li M, Hou X, Zheng L, et al. Utilizing phenotypic characteristics of metastatic brain tumors to improve the probability of detecting circulating tumor DNA from cerebrospinal fluid in non-small-cell lung cancer patients: development and validation of a prediction model in a prospective cohort study. ESMO Open. 2022; 7(1): 100305.

[68] Xie N, Tian C, Wu H, et al. FGFR aberrations increase the risk of brain metastases and predict poor prognosis in metastatic breast cancer patients. Ther Adv Med Oncol. 2020; 12: 1758835920915305.

[69] Alder L, Broadwater G, Green M, et al. Unique genomic alterations in the circulating tumor DNA of patients with solid tumors brain metastases. Neurooncol Adv. 2024; 6(1): vdae052.

[70] Curtaz CJ, Reifschlager L, Strahle L, et al. Analysis of microRNAs in exosomes of breast cancer patients in search of molecular prognostic factors in brain metastases. Int J Mol Sci. 2022; 23(7): 3683.

[71] Chen Z, Wang X, Jin Z, et al. Deep learning on tertiary lymphoid structures in hematoxylin-eosin predicts cancer prognosis and immunotherapy response. NPJ Precis Oncol. 2024; 8(1): 73.

[72] Zhao YY, Fan Z, Tao BR, Du ZG, Shi ZF. Density of tertiary lymphoid structures predicts clinical outcome in breast cancer brain metastasis. J Immunother Cancer. 2024; 12(7): e009232.

[73] You Y, Lai X, Pan Y, et al. Artificial intelligence in cancer target identification and drug discovery. Signal Transduct Target Ther. 2022; 7(1): 156.

[74] Elemento O, Leslie C, Lundin J, Tourassi G. Artificial intelligence in cancer research, diagnosis and therapy. Nat Rev Cancer. 2021; 21(12): 747-752.

[75] Deng F, Liu Z, Fang W, et al. MRI radiomics for brain metastasis sub-pathology classification from non-small cell lung cancer: a machine learning, multicenter study. Phys Eng Sci Med. 2023; 46(3): 1309-1320.

[76] Janitri V, ArulJothi KN, Ravi Mythili VM, et al. The roles of patient-derived xenograft models and artificial intelligence toward precision medicine. MedComm. 2024; 5(10): e745.

[77] Gong J, Wang T, Wang Z, et al. Enhancing brain metastasis prediction in non-small cell lung cancer: a deep learning-based segmentation and CT radiomics-based ensemble learning model. Cancer Imaging. 2024; 24(1): 1.

[78] Gao P, Shan W, Guo Y, et al. Development and validation of a deep learning model for brain tumor diagnosis and classification using magnetic resonance imaging. JAMA Netw Open. 2022; 5(8): e2225608.

[79] Zhou Z, Sanders JW, Johnson JM, et al. Computer-aided detection of brain metastases in T1-weighted MRI for stereotactic radiosurgery using deep learning single-shot detectors. Radiology. 2020; 295(2): 407-415.

[80] Wang TW, Hsu MS, Lee WK, et al. Brain metastasis tumor segmentation and detection using deep learning algorithms: a systematic review and meta-analysis. Radiother Oncol. 2024; 190: 110007.

[81] Cho SJ, Sunwoo L, Baik SH, Bae YJ, Choi BS, Kim JH. Brain metastasis detection using machine learning: a systematic review and meta-analysis. Neuro Oncol. 2021; 23(2): 214-225.

[82] Kikinis R, Wells WM, 3rd. Detection of brain metastases with deep learning single-shot detector algorithms. Radiology. 2020; 295(2): 416-417.

[83] Yun S, Park JE, Kim N, Park SY, Kim HS. Reducing false positives in deep learning-based brain metastasis detection by using both gradient-echo and spin-echo contrast-enhanced MRI: validation in a multi-center diagnostic cohort. Eur Radiol. 2024; 34(5): 2873-2884.

[84] Jiao T, Li F, Cui Y, et al. Deep learning with an attention mechanism for differentiating the origin of brain metastasis using MR images. J Magn Reson Imaging. 2023; 58(5): 1624-1635.

[85] Zhou H, Watson M, Bernadt CT, et al. AI-guided histopathology predicts brain metastasis in lung cancer patients. J Pathol. 2024; 263(1): 89-98.

[86] Li Y, Lv X, Chen C, et al. A deep learning model integrating multisequence MRI to predict EGFR mutation subtype in brain metastases from non-small cell lung cancer. Eur Radiol Exp. 2024; 8(1): 2.

[87] Jeong H, Park JE, Kim N, Yoon SK, Kim HS. Deep learning-based detection and quantification of brain metastases on black-blood imaging can provide treatment suggestions: a clinical cohort study. Eur Radiol. 2024; 34(3): 2062-2071.

[88] Zhou Z, Wang M, Zhao R, et al. A multi-task deep learning model for EGFR genotyping prediction and GTV segmentation of brain metastasis. J Transl Med. 2023; 21(1): 788.

[89] Haim O, Abramov S, Shofty B, et al. Predicting EGFR mutation status by a deep learning approach in patients with non-small cell lung cancer brain metastases. J Neurooncol. 2022; 157(1): 63-69.

[90] Xue J, Wang B, Ming Y, et al. Deep learning-based detection and segmentation-assisted management of brain metastases. Neuro Oncol. 2020; 22(4): 505-514.

[91] Jalalifar SA, Soliman H, Sahgal A, Sadeghi-Naini A. Predicting the outcome of radiotherapy in brain metastasis by integrating the clinical and MRI-based deep learning features. Med Phys. 2022; 49(11): 7167-7178.

[92] Jalalifar SA, Soliman H, Sahgal A, Sadeghi-Naini A. A self-attention-guided 3D deep residual network with big transfer to predict local failure in brain metastasis after radiotherapy using multi-channel MRI. IEEE J Transl Eng Health Med. 2023; 11: 13-22.

[93] Cho SJ, Cho W, Choi D, et al. Prediction of treatment response after stereotactic radiosurgery of brain metastasis using deep learning and radiomics on longitudinal MRI data. Sci Rep. 2024; 14(1): 11085.

[94] Jalalifar SA, Soliman H, Sahgal A, Sadeghi-Naini A. Automatic assessment of stereotactic radiation therapy outcome in brain metastasis using longitudinal segmentation on serial MRI. IEEE J Biomed Health Inform. 2023; 27(6): 2681-2692.

[95] Rammohan N, Ho A, Besson P, Kruser TJ, Bandt SK. Whole-brain radiotherapy associated with structural changes resembling aging as determined by anatomic surface-based deep learning. Neuro Oncol. 2023; 25(7): 1323-1330.

[96] Lu CF, Liao CY, Chao HS, et al. A radiomics-based deep learning approach to predict progression free-survival after tyrosine kinase inhibitor therapy in non-small cell lung cancer. Cancer Imaging. 2023; 23(1): 9.

[97] Wang TW, Chao HS, Chiu HY, et al. Radiomics of metastatic brain tumor as a predictive image biomarker of progression-free survival in patients with non-small-cell lung cancer with brain metastasis receiving tyrosine kinase inhibitors. Transl Oncol. 2024; 39: 101826.

[98] Wu Y, Kang K, Han C, Wang L, Wang Z, Zhao A. Single-cell profiling comparisons of tumor microenvironment between primary advanced lung adenocarcinomas and brain metastases and machine learning algorithms in predicting immunotherapeutic responses. Biomolecules. 2023; 13(1): 185.

[99] Martini ML, Oermann EK. Intraoperative brain tumour identification with deep learning. Nat Rev Clin Oncol. 2020; 17(4): 200-201.

[100] Hollon TC, Pandian B, Adapa AR, et al. Near real-time intraoperative brain tumor diagnosis using stimulated Raman histology and deep neural networks. Nat Med. 2020; 26(1): 52-58.

[101] Liu Z, Duan T, Zhang Y, et al. Radiogenomics: a key component of precision cancer medicine. Br J Cancer. 2023; 129(5): 741-753.

[102] Sun Y, Zhang Y, Gan J, et al. Comprehensive quantitative radiogenomic evaluation reveals novel radiomic subtypes with distinct immune pattern in glioma. Comput Biol Med. 2024; 177: 108636.

[103] Wu Q, Sun MS, Liu YH, Ye JM, Xu L. Development and external validation of a prediction model for brain metastases in patients with metastatic breast cancer. J Cancer Res Clin Oncol. 2023; 149(13): 12333-12353.

[104] Young JR, Ressler JA, Shiroishi MS, et al. Association of relative cerebral blood volume from dynamic susceptibility contrast-enhanced perfusion MR with HER2 status in breast cancer brain metastases. Acad Radiol. 2023; 30(9): 1816-1822.

[105] Luo X, Xie H, Yang Y, et al. Radiomic signatures for predicting receptor status in breast cancer brain metastases. Front Oncol. 2022; 12: 878388.

[106] Young JR, Ressler JA, Mortimer JE, Schmolze D, Fitzgibbons M, Chen BT. Performance of enhancement on brain MRI for identifying HER2 overexpression in breast cancer brain metastases. Eur J Radiol. 2021; 144: 109948.

[107] Strotzer QD, Wagner T, Angstwurm P, et al. Limited capability of MRI radiomics to predict primary tumor histology of brain metastases in external validation. Neurooncol Adv. 2024; 6(1): vdae060.

[108] Li C, Liu M, Zhang Y, et al. Novel models by machine learning to predict prognosis of breast cancer brain metastases. J Transl Med. 2023; 21(1): 404.

[109] Pandey S, Kutuk T, Abdalah MA, et al. Prediction of radiologic outcome-optimized dose plans and post-treatment magnetic resonance images: A proof-of-concept study in breast cancer brain metastases treated with stereotactic radiosurgery. Phys Imaging Radiat Oncol. 2024; 31: 100602.

[110] Shahamatdar S, Saeed-Vafa D, Linsley D, et al. Deceptive learning in histopathology. Histopathology. 2024; 85(1): 116-132.

[111] Pellerino A, Bruno F, Ruda R, Soffietti R. Systemic therapy for lung cancer brain metastases. Curr Treat Options Oncol. 2021; 22(12): 110.

[112] Hsu PC, Chiu LC, Chen KT, et al. Clinical outcome analysis of non-small cell lung cancer patients with brain metastasis receiving metastatic brain tumor resection surgery: a multicenter observational study. Am J Cancer Res. 2023; 13(8): 3607-3617.

[113] Winther RR, Hjermstad MJ, Skovlund E, et al. Surgery for brain metastases-impact of the extent of resection. Acta Neurochir (Wien). 2022; 164(10): 2773-2780.

[114] Wasilewski D, Radke J, Xu R, et al. Effectiveness of immune checkpoint inhibition vs chemotherapy in combination with radiation therapy among patients with non-small cell lung cancer and brain metastasis undergoing neurosurgical resection. JAMA Netw Open. 2022; 5(4): e229553.

[115] Peng Y, Zhao Q, Liao Z, Ma Y, Ma D. Efficacy and safety of first-line treatments for patients with advanced anaplastic lymphoma kinase mutated, non-small cell cancer: A systematic review and network meta-analysis. Cancer. 2023; 129(8): 1261-1275.

[116] Yang Y, Min J, Yang N, et al. Envonalkib versus crizotinib for treatment-naive ALK-positive non-small cell lung cancer: a randomized, multicenter, open-label, phase III trial. Signal Transduct Target Ther. 2023; 8(1): 301.

[117] Liu G, Lam VK. Podcast on lorlatinib as a first-line treatment option for patients with ALK-positive metastatic NSCLC with brain metastasis. Adv Ther. 2023; 40(10): 4117-4126.

[118] De Carlo E, Bertoli E, Del Conte A, et al. Brain metastases management in oncogene-addicted non-small cell lung cancer in the targeted therapies era. Int J Mol Sci. 2022; 23(12): 6477.

[119] Niu L, Wu H, Gao R, et al. Optimal sequence of LT for symptomatic BM in EGFR-mutant NSCLC: a comparative study of first-line EGFR-TKIs with/without upfront LT. J Cancer Res Clin Oncol. 2024; 150(2): 94.

[120] de Langen AJ, Johnson ML, Mazieres J, et al. Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRAS(G12C) mutation: a randomised, open-label, phase 3 trial. Lancet. 2023; 401(10378): 733-746.

[121] Wang M, Fan Y, Sun M, et al. Sunvozertinib for patients in China with platinum-pretreated locally advanced or metastatic non-small-cell lung cancer and EGFR exon 20 insertion mutation (WU-KONG6): single-arm, open-label, multicentre, phase 2 trial. Lancet Respir Med. 2024; 12(3): 217-224.

[122] Zeng Y, Su X, Zhao Y, et al. Rationale and value of consolidative cranial local therapy in EGFR-mutant non-small cell lung cancer patients with baseline brain metastasis treated with first-line EGFR-TKIs. Ther Adv Med Oncol. 2023; 15: 17588359231169975.

[123] Villaruz LC, Wang X, Bertino EM, et al. A single-arm, multicenter, phase II trial of osimertinib in patients with epidermal growth factor receptor exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations. ESMO Open. 2023; 8(2): 101183.

[124] Gaebe K, Li AY, Park A, et al. Stereotactic radiosurgery versus whole brain radiotherapy in patients with intracranial metastatic disease and small-cell lung cancer: a systematic review and meta-analysis. Lancet Oncol. 2022; 23(7): 931-939.

[125] de Ruiter MB, Groot PFC, Deprez S, et al. Hippocampal avoidance prophylactic cranial irradiation (HA-PCI) for small cell lung cancer reduces hippocampal atrophy compared to conventional PCI. Neuro Oncol. 2023; 25(1): 167-176.

[126] Ning J, Chen L, Zeng Y, et al. The scheme, and regulative mechanism of pyroptosis, ferroptosis, and necroptosis in radiation injury. Int J Biol Sci. 2024; 20(5): 1871-1883.

[127] Yu NY, Sio TT, Ernani V, Savvides P, Schild SE. Role of prophylactic cranial irradiation in extensive-stage small cell lung cancer. J Natl Compr Canc Netw. 2021; 19(12): 1465-1469.

[128] Cherng HR, Sun K, Bentzen S, et al. Evaluating the heterogeneity of hippocampal avoidant whole brain radiotherapy treatment effect: A secondary analysis of NRG CC001. Neuro Oncol. 2024; 26(5): 911-921.

[129] Bodensohn R, Kaempfel AL, Boulesteix AL, et al. Stereotactic radiosurgery versus whole-brain radiotherapy in patients with 4–10 brain metastases: A nonrandomized controlled trial. Radiother Oncol. 2023; 186: 109744.

[130] Lin B, Huang D, Du H, et al. Whole-brain radiation therapy with simultaneous integrated boost versus whole-brain radiation therapy plus stereotactic radiosurgery for the treatment of brain metastasis from lung cancer. Front Oncol. 2021; 11: 631422.

[131] Dong X, Wang K, Yang H, et al. Choice of radiotherapy modality for the combined treatment of non-small cell lung cancer with brain metastases: whole-brain radiation therapy with simultaneous integrated boost or stereotactic radiosurgery. Front Oncol. 2023; 13: 1220047.

[132] Ni M, Liu W, Jiang A, et al. Whole brain radiation therapy plus focal radiation boost may generate better survival benefit for brain metastases from non-small cell lung cancer. Front Oncol. 2020; 10: 576700.

[133] Nieder C, Aanes SG, Haukland E. Primary systemic therapy for patients with brain metastases from lung cancer ineligible for targeted agents. J Cancer Res Clin Oncol. 2022; 148(11): 3109-3116.

[134] Chen L, Li Y, Dong X, et al. The value of postoperative radiotherapy in thymoma patients with myasthenia gravis. Radiother Oncol. 2023; 183: 109644.

[135] Wang X, Song B, Wang Z, Qin L, Liang W. The innovative design of a delivery and real-time tracer system for anti-encephalitis drugs that can penetrate the blood-brain barrier. J Control Release. 2023; 363: 136-148.

[136] Jenkins S, Zhang W, Steinberg SM, et al. Phase I study and cell-free DNA analysis of T-DM1 and metronomic temozolomide for secondary prevention of HER2-positive breast cancer brain metastases. Clin Cancer Res. 2023; 29(8): 1450-1459.

[137] Nadal E, Rodriguez-Abreu D, Simo M, et al. Phase II trial of atezolizumab combined with carboplatin and pemetrexed for patients with advanced nonsquamous non-small-cell lung cancer with untreated brain metastases (atezo-brain, GECP17/05). J Clin Oncol. 2023; 41(28): 4478-4485.

[138] Zhou Q, Xu CR, Cheng Y, et al. Bevacizumab plus erlotinib in Chinese patients with untreated, EGFR-mutated, advanced NSCLC (ARTEMIS-CTONG1509): A multicenter phase 3 study. Cancer Cell. 2021; 39(9): 1279-1291. e3.

[139] Hou X, Li M, Wu G, et al. Gefitinib plus chemotherapy vs gefitinib alone in untreated EGFR-mutant non-small cell lung cancer in patients with brain metastases: the GAP BRAIN open-label, randomized, multicenter, phase 3 study. JAMA Netw Open. 2023; 6(2): e2255050.

[140] Rios-Hoyo A, Arriola E. Immunotherapy and brain metastasis in lung cancer: connecting bench side science to the clinic. Front Immunol. 2023; 14: 1221097.

[141] Chu X, Tian W, Ning J, Zhou R. Efficacy and safety of personalized optimal PD-(L)1 combinations in advanced NSCLC: a network Meta-Analysis. J Natl Cancer Inst. 2024; 116(10): 1571-1586.

[142] Tsakonas G, Ekman S, Koulouris A, Adderley H, Ackermann CJ, Califano R. Safety and efficacy of immune checkpoint blockade in patients with advanced nonsmall cell lung cancer and brain metastasis. Int J Cancer. 2023; 153(9): 1556-1567.

[143] Descourt R, Greillier L, Perol M, et al. First-line single-agent pembrolizumab for PD-L1-positive (tumor proportion score >/= 50%) advanced non-small cell lung cancer in the real world: impact in brain metastasis: a national French multicentric cohort (ESCKEYP GFPC study). Cancer Immunol Immunother. 2023; 72(1): 91-99.

[144] Kemmotsu N, Ninomiya K, Kunimasa K, et al. Low frequency of intracranial progression in advanced NSCLC patients treated with cancer immunotherapies. Int J Cancer. 2024; 154(1): 169-179.

[145] Abdulhaleem M, Johnston H, D’Agostino R, Jr., et al. Local control outcomes for combination of stereotactic radiosurgery and immunotherapy for non-small cell lung cancer brain metastases. J Neurooncol. 2022; 157(1): 101-107.

[146] Ma JC, Zhang JX, Wang F, Yu J, Chen D. The effect of immunotherapy on oligometastatic non-small cell lung cancer patients by sites of metastasis. Front Immunol. 2022; 13: 1039157.

[147] Phillips W, Thornton Z, Andrews L, et al. Efficacy of PD-1/PD-L1 immunotherapy on brain metastatic non-small-cell lung cancer and treatment-related adverse events: a systematic review. Crit Rev Oncol Hematol. 2024; 196: 104288.

[148] Reck M, Ciuleanu TE, Lee JS, et al. Systemic and intracranial outcomes with first-line nivolumab plus ipilimumab in patients with metastatic NSCLC and baseline brain metastases from CheckMate 227 Part 1. J Thorac Oncol. 2023; 18(8): 1055-1069.

[149] Chu X, Niu L, Xiao G, et al. The long-term and short-term efficacy of immunotherapy in non-small cell lung cancer patients with brain metastases: a systematic review and meta-analysis. Front Immunol. 2022; 13: 875488.

[150] Jiang JM, Kabarriti R, Brodin NP, et al. Stereotactic radiosurgery with immunotherapy is associated with improved overall survival in patients with metastatic melanoma or non-small cell lung cancer: a National Cancer Database analysis. Clin Transl Oncol. 2022; 24(1): 104-111.

[151] Yu Y, Chen H, Tian Z, et al. Improved survival outcome with not-delayed radiotherapy and immediate PD-1/PD-L1 inhibitor for non-small-cell lung cancer patients with brain metastases. J Neurooncol. 2023; 165(1): 127-137.

[152] Li J, Li W, Xu S, Zhu H. Brain injury after cranial radiotherapy combined with immunotherapy for brain metastases in lung cancer: a retrospective study. Future Oncol. 2023; 19(13): 947-959.

[153] Luo S, Li P, Zhang A, et al. G-CSF improving combined whole brain radiotherapy and immunotherapy prognosis of non-small cell lung cancer brain metastases. Int Immunopharmacol. 2024; 130: 111705.

[154] Sereno M, Hernandez de Cordoba I, Gutierrez-Gutierrez G, Casado E. Brain metastases and lung cancer: molecular biology, natural history, prediction of response and efficacy of immunotherapy. Front Immunol. 2023; 14: 1297988.

[155] Tian W, Chu X, Tanzhu G, Zhou R. Optimal timing and sequence of combining stereotactic radiosurgery with immune checkpoint inhibitors in treating brain metastases: clinical evidence and mechanistic basis. J Transl Med. 2023; 21(1): 244.

[156] Ma J, Tian Y, Hao S, et al. Outcomes of first-line anti-PD-L1 blockades combined with brain radiotherapy for extensive-stage small-cell lung cancer with brain metastasis. J Neurooncol. 2022; 159(3): 685-693.

[157] Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019; 394(10212): 1929-1939.

[158] Goldman JW, Dvorkin M, Chen Y, et al. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021; 22(1): 51-65.

[159] Horn L, Mansfield AS, Szczesna A, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018; 379(23): 2220-2229.

[160] Cheng Y, Han L, Wu L, et al. Effect of first-line serplulimab vs placebo added to chemotherapy on survival in patients with extensive-stage small cell lung cancer: the ASTRUM-005 randomized clinical trial. JAMA. 2022; 328(12): 1223-1232.

[161] Zhou F, Zhao W, Gong X, et al. Immune-checkpoint inhibitors plus chemotherapy versus chemotherapy as first-line treatment for patients with extensive-stage small cell lung cancer. J Immunother Cancer. 2020; 8(2): e001300.

[162] Huang L, Chen S, Liu H, et al. PD-L1 inhibitors combined with whole brain radiotherapy in patients with small cell lung cancer brain metastases: Real-world evidence. Cancer Med. 2024; 13(7): e7125.

[163] Lu S, Guo X, Li Y, Liu H, Zhang Y, Zhu H. Antiprogrammed death ligand 1 therapy failed to reduce the risk of developing brain metastases in patients with extensive-stage small cell lung cancer: a retrospective analysis. Cancer. 2024; 130(1): 18-30.

[164] Chang J, Jing X, Hua Y, et al. Programmed cell death 1 pathway inhibitors improve the overall survival of small cell lung cancer patients with brain metastases. J Cancer Res Clin Oncol. 2023; 149(5): 1825-1833.

[165] Yu HA, Goto Y, Hayashi H, et al. HERTHENA-Lung01, a phase II trial of patritumab deruxtecan (HER3-DXd) in epidermal growth factor receptor-mutated non-small-cell lung cancer after epidermal growth factor receptor tyrosine kinase inhibitor therapy and platinum-based chemotherapy. J Clin Oncol. 2023; 41(35): 5363-5375.

[166] Perol M, Solomon BJ, Goto K, et al. CNS protective effect of selpercatinib in first-line RET fusion-positive advanced non-small cell lung cancer. J Clin Oncol. 2024; 42(21): 2500-2505.

[167] Solomon BJ, Bauer TM, Mok TSK, et al. Efficacy and safety of first-line lorlatinib versus crizotinib in patients with advanced, ALK-positive non-small-cell lung cancer: updated analysis of data from the phase 3, randomised, open-label CROWN study. Lancet Respir Med. 2023; 11(4): 354-366.

[168] Ahn MJ, Kim HR, Yang JCH, et al. Efficacy and safety of brigatinib compared with crizotinib in Asian vs. non-Asian patients with locally advanced or metastatic ALK-inhibitor-naive ALK+ non-small cell lung cancer: final results from the phase III ALTA-1L study. Clin Lung Cancer. 2022; 23(8): 720-730.

[169] Solomon BJ, Bauer TM, Ignatius Ou SH, et al. Post hoc analysis of lorlatinib intracranial efficacy and safety in patients with ALK-Positive advanced non-small-cell lung cancer from the phase III CROWN study. J Clin Oncol. 2022; 40(31): 3593-3602.

[170] Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in ALK inhibitor-naive advanced ALK-positive NSCLC: final results of phase 3 ALTA-1L trial. J Thorac Oncol. 2021; 16(12): 2091-2108.

[171] Horn L, Wang Z, Wu G, et al. Ensartinib vs crizotinib for patients with anaplastic lymphoma kinase-positive non-small cell lung cancer: a randomized clinical trial. JAMA Oncol. 2021; 7(11): 1617-1625.

[172] Tu HY, Feng J, Shi M, et al. A phase IIIb open-label, single-arm study of afatinib in EGFR TKI-naive patients with EGFRm+ NSCLC: final analysis, with a focus on patients enrolled at sites in China. Target Oncol. 2022; 17(1): 1-13.

[173] de Marinis F, Laktionov KK, Poltoratskiy A, et al. Afatinib in EGFR TKI-naive patients with locally advanced or metastatic EGFR mutation-positive non-small cell lung cancer: Interim analysis of a Phase 3b study. Lung Cancer. 2021; 152: 127-134.

[174] Zhou HQ, Zhang YX, Chen G, et al. Gefitinib (an EGFR tyrosine kinase inhibitor) plus anlotinib (an multikinase inhibitor) for untreated, EGFR-mutated, advanced non-small cell lung cancer (FL-ALTER): a multicenter phase III trial. Signal Transduct Target Ther. 2024; 9(1): 215.

[175] Janne PA, Planchard D, Kobayashi K, et al. CNS efficacy of osimertinib with or without chemotherapy in epidermal growth factor receptor-mutated advanced non-small-cell lung cancer. J Clin Oncol. 2024; 42(7): 808-820.

[176] Rudin CM, Liu SV, Soo RA, et al. SKYSCRAPER-02: tiragolumab in combination with atezolizumab plus chemotherapy in untreated extensive-stage small-cell lung cancer. J Clin Oncol. 2024; 42(3): 324-335.

[177] Ready NE, Audigier-Valette C, Goldman JW, et al. First-line nivolumab plus ipilimumab for metastatic non-small cell lung cancer, including patients with ECOG performance status 2 and other special populations: CheckMate 817. J Immunother Cancer. 2023; 11(2): e006127.

[178] Investigators HA-AS, Fang W, Zhao Y, et al. Ivonescimab plus chemotherapy in non-small cell lung cancer with EGFR variant: a randomized clinical trial. JAMA. 2024; 332(7): 561-570.

[179] Zeng M, Verma V, Chen X, et al. Stereotactic radiotherapy vs whole brain radiation therapy in EGFR mutated NSCLC: Results & reflections from the prematurely closed phase III HYBRID trial. Radiother Oncol. 2024; 197: 110334.

[180] Yang Z, Zhang Y, Li R, et al. Whole-brain radiotherapy with and without concurrent erlotinib in NSCLC with brain metastases: a multicenter, open-label, randomized, controlled phase III trial. Neuro Oncol. 2021; 23(6): 967-978.

[181] Hurvitz SA, Kim SB, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer patients with brain metastases from the randomized DESTINY-Breast03 trial. ESMO Open. 2024; 9(5): 102924.

[182] Tripathy D, Tolaney SM, Seidman AD, et al. Treatment with etirinotecan pegol for patients with metastatic breast cancer and brain metastases: final results from the phase 3 ATTAIN randomized clinical trial. JAMA Oncol. 2022; 8(7): 1047-1052.

[183] Dai MS, Feng YH, Chen SW, et al. Analysis of the pan-Asian subgroup of patients in the NALA Trial: a randomized phase III NALA Trial comparing neratinib+capecitabine (N+C) vs lapatinib+capecitabine (L+C) in patients with HER2+metastatic breast cancer (mBC) previously treated with two or more HER2-directed regimens. Breast Cancer Res Treat. 2021; 189(3): 665-676.

[184] Hurvitz SA, Saura C, Oliveira M, et al. Efficacy of neratinib plus capecitabine in the subgroup of patients with central nervous system involvement from the NALA trial. Oncologist. 2021; 26(8): e1327-e1338.

[185] Shi Y, Chen G, Wang X, et al. Central nervous system efficacy of furmonertinib (AST2818) versus gefitinib as first-line treatment for EGFR-mutated NSCLC: results From the FURLONG study. J Thorac Oncol. 2022; 17(11): 1297-1305.

[186] Ersoy TF, Brainman D, Coras R, et al. Defining the role of surgery for patients with multiple brain metastases. J Neurooncol. 2024; 169(2): 317-328.

[187] Sarkis HM, Zawy Alsofy S, Stroop R, et al. Does 5-ALA fluorescence microscopy improve complete resectability in cerebral/cerebellar metastatic surgery? A retrospective data analysis from a cranial center. Cancers (Basel). 2024; 16(12): 2242.

[188] Hanalis-Miller T, Ricon-Becker I, Sakis N, et al. Peri-operative individually tailored psychological intervention in breast cancer patients improves psychological indices and molecular biomarkers of metastasis in excised tumors. Brain Behav Immun. 2024; 117: 529-540.

[189] Hijazi A, Mohanna M, Sabbagh S, et al. Clinico-pathologic factors and survival of patients with breast cancer diagnosed with de novo brain metastasis: a national cancer database analysis. Breast Cancer Res Treat. 2024; 206(3): 527-541.

[190] Onder T, Karacin C. Effect of HER2-low status on brain metastasis-free survival and survival after brain metastasis in patients with breast cancer. Clin Transl Oncol. 2024.

[191] Nakayama T, Niikura N, Yamanaka T, et al. Trastuzumab deruxtecan for the treatment of patients with HER2-positive breast cancer with brain and/or leptomeningeal metastases: an updated overall survival analysis using data from a multicenter retrospective study (ROSET-BM). Breast Cancer. 2024; 31(6): 1167-1175.

[192] Rogawski D, Cao T, Ma Q, et al. Durable responses to trastuzumab deruxtecan in patients with leptomeningeal metastases from breast cancer with variable HER2 expression. J Neurooncol. 2024; 170(1): 209-217.

[193] Jerusalem G, Park YH, Yamashita T, et al. Trastuzumab deruxtecan in HER2-positive metastatic breast cancer patients with brain metastases: a DESTINY-Breast01 subgroup analysis. Cancer Discov. 2022; 12(12): 2754-2762.

[194] Michelon I, Vilbert M, Marinho AD, et al. Trastuzumab deruxtecan in human epidermal growth factor receptor 2-positive breast cancer brain metastases: a systematic review and meta-analysis. ESMO Open. 2024; 9(2): 102233.

[195] Jacobson A. Trastuzumab deruxtecan improves progression-free survival and intracranial response in patients with HER2-positive metastatic breast cancer and brain metastases. Oncologist. 2022; 27(Suppl 1): S3-S4.

[196] Freedman RA, Heiling HM, Li T, et al. Neratinib and ado-trastuzumab emtansine for pretreated and untreated human epidermal growth factor receptor 2 (HER2)-positive breast cancer brain metastases: Translational Breast Cancer Research Consortium trial 022. Ann Oncol. 2024; 35(11): 993-1002.

[197] Gu Q, Zhu M, Wang Y, Gu Y. Retrospective analysis of pyrotinib-based therapy for metastatic breast cancer: promising efficacy in combination with trastuzumab. Breast Cancer (Dove Med Press). 2024; 16: 253-268.

[198] Yan M, Ouyang Q, Sun T, et al. Pyrotinib plus capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases (PERMEATE): a multicentre, single-arm, two-cohort, phase 2 trial. Lancet Oncol. 2022; 23(3): 353-361.

[199] Mikaeili Namini A, Jahangir M, Mohseni M, et al. An in silico comparative transcriptome analysis identifying hub lncRNAs and mRNAs in brain metastatic small cell lung cancer (SCLC). Sci Rep. 2022; 12(1): 18063.

[200] Nader-Marta G, Martins-Branco D, Agostinetto E, et al. Efficacy of tyrosine kinase inhibitors for the treatment of patients with HER2-positive breast cancer with brain metastases: a systematic review and meta-analysis. ESMO Open. 2022; 7(3): 100501.

[201] Chen D, Xu F, Lu Y, et al. Pyrotinib and trastuzumab plus palbociclib and fulvestrant in HR+/HER2+ breast cancer patients with brain metastasis. NPJ Breast Cancer. 2024; 10(1): 45.

[202] Frenel JS, Zeghondy J, Guerin-Charbonnel C, et al. tucatinib combination treatment after trastuzumab-deruxtecan in patients with ERBB2-positive metastatic breast cancer. JAMA Netw Open. 2024; 7(4): e244435.

[203] Huo X, Shen G, Wang T, et al. Treatment options for patients with human epidermal growth factor 2-positive breast cancer brain metastases: A systematic review and meta-analysis. Front Oncol. 2023; 13: 1003565.

[204] Estermann A, Schneider C, Zimmermann F, Papachristofilou A, Finazzi T. Whole brain radiation therapy for patients with brain metastases: survival outcomes and prognostic factors in a contemporary institutional series. Strahlenther Onkol. 2024; 200(11): 942-948.

[205] Zhang H, Wu Q, Li L, Wang L, Zhong Y. Whole-brain radiation therapy plus simultaneous integrated boost for brain metastases from breast cancers. PeerJ. 2024; 12: e17696.

[206] Konopka-Filippow M, Hempel D, Sierko E. Actual, personalized approaches to preserve cognitive functions in brain metastases breast cancer patients. Cancers (Basel). 2022; 14(13): 3119.

[207] Gao C, Wang F, Suki D, et al. Effects of systemic therapy and local therapy on outcomes of 873 breast cancer patients with metastatic breast cancer to brain: MD Anderson Cancer Center experience. Int J Cancer. 2021; 148(4): 961-970.

[208] Turna M, Yildirim BA, Numanoglu C, Akboru MH, Rzazade R, Caglar HB. Comprehensive analysis of stereotactic Radiosurgery outcomes in triple-negative breast cancer patients with brain metastases: The influence of immunotherapy and prognostic factors. Breast. 2024; 76: 103757.

[209] Kowalchuk RO, Niranjan A, Hess J, et al. Stereotactic radiosurgery and local control of brain metastases from triple-negative breast cancer. J Neurosurg. 2023; 138(6): 1608-1614.

[210] Alzate JD, Mashiach E, Berger A, et al. Low-dose radiosurgery for brain metastases in the era of modern systemic therapy. Neurosurgery. 2023; 93(5): 1112-1120.

[211] Gagliardi F, De Domenico P, Snider S, Nizzola MG, Mortini P. Efficacy of neoadjuvant stereotactic radiotherapy in brain metastases from solid cancer: a systematic review of literature and meta-analysis. Neurosurg Rev. 2023; 46(1): 130.

[212] Khatri VM, Mills MN, Oliver DE, et al. Tucatinib and stereotactic radiosurgery in the management of HER2 positive breast cancer brain metastases. J Neurooncol. 2023; 164(1): 191-197.

[213] Pikis S, Mantziaris G, Protopapa M, et al. Stereotactic radiosurgery for brain metastases from human epidermal receptor 2 positive breast Cancer: an international, multi-center study. J Neurooncol. 2024; 170(1): 199-208.

[214] Tang L, Zhang W, Chen L. Brain radiotherapy combined with targeted therapy for HER2-positive breast cancer patients with brain metastases. Breast Cancer (Dove Med Press). 2024; 16: 379-392.

[215] Chun SJ, Kim K, Kim YB, et al. Risk of radionecrosis in HER2-positive breast cancer with brain metastasis receiving trastuzumab emtansine (T-DM1) and brain stereotactic radiosurgery. Radiother Oncol. 2024; 199: 110461.

[216] Koide Y, Nagai N, Adachi S, et al. Impact of concurrent antibody-drug conjugates and radiotherapy on symptomatic radiation necrosis in breast cancer patients with brain metastases: a multicenter retrospective study. J Neurooncol. 2024; 168(3): 415-423.

[217] Tian W, Hao S, Wang L, Chen Y, Li Z, Luo D. Pyrotinib treatment enhances the radiosensitivity in HER2-positive brain metastatic breast cancer patients. Anticancer Drugs. 2022; 33(1): e622-e627.

[218] Anwar M, Chen Q, Ouyang D, et al. Pyrotinib treatment in patients with HER2-positive metastatic breast cancer and brain metastasis: exploratory final analysis of real-world, multicenter data. Clin Cancer Res. 2021; 27(16): 4634-4641.

[219] Dai L, Gao T, Guo R, et al. Efficacy and safety of pyrotinib-based regimens in HER2 positive metastatic breast cancer: A retrospective real-world data study. Neoplasia. 2024; 56: 101029.

[220] Huang J, Sun S, Tan Q, et al. Effectiveness and Safety of pyrotinib-based therapy in the treatment of HER2-positive breast cancer patients with brain metastases: a multicenter real-world study. Clin Breast Cancer. 2024; 24(6): e509-e518. e1.

[221] Huang J, Zhu W, Duan Q, et al. Efficacy and safety of radiotherapy combined with pyrotinib in the treatment of HER2-positive breast cancer with brain metastases. Breast Cancer (Dove Med Press). 2023; 15: 841-853.

[222] Chew SM, Ferraro E, Safonov A, et al. Impact of cyclin dependent kinase 4/6 inhibitors on breast cancer brain metastasis outcomes. Eur J Cancer. 2024; 207: 114175.

[223] Kubeczko M, Jarzab M, Krzywon A, Graupner D, Polakiewicz-Gilowska A, Gabrys D. Efficacy of CDK 4/6 inhibitors and radiotherapy in breast cancer patients with brain metastases. J Clin Med. 2023; 12(5): 2044.

[224] Nayyar N, de Sauvage MA, Chuprin J, et al. CDK4/6 inhibition sensitizes intracranial tumors to PD-1 blockade in preclinical models of brain metastasis. Clin Cancer Res. 2024; 30(2): 420-435.

[225] Zhou S, Xie J, Huang Z, et al. Anti-PD-(L)1 immunotherapy for brain metastases in non-small cell lung cancer: Mechanisms, advances, and challenges. Cancer Lett. 2021; 502: 166-179.

[226] Failing JJ, Aubry MC, Mansfield AS. Human leukocyte antigen expression in paired primary lung tumors and brain metastases in non-small cell lung cancer. Cancer Immunol Immunother. 2021; 70(1): 215-219.

[227] Xiao G, Liu Z, Gao X, et al. Immune checkpoint inhibitors for brain metastases in non-small-cell lung cancer: from rationale to clinical application. Immunotherapy. 2021; 13(12): 1031-1051.

[228] Zhao P, Zhang J, Wu A, et al. Biomimetic codelivery overcomes osimertinib-resistant NSCLC and brain metastasis via macrophage-mediated innate immunity. J Control Release. 2021; 329: 1249-1261.

[229] Biswas AK, Han S, Tai Y, et al. Targeting S100A9-ALDH1A1-retinoic acid signaling to suppress brain relapse in EGFR-mutant lung cancer. Cancer Discov. 2022; 12(4): 1002-1021.

[230] Monteiro C, Miarka L, Perea-Garcia M, et al. Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism. Nat Med. 2022; 28(4): 752-765.

[231] Martinez-Reyes I, Chandel NS. Cancer metabolism: looking forward. Nat Rev Cancer. 2021; 21(10): 669-680.

[232] Liu W, Zhou Y, Duan W, et al. Glutathione peroxidase 4-dependent glutathione high-consumption drives acquired platinum chemoresistance in lung cancer-derived brain metastasis. Clin Transl Med. 2021; 11(9): e517.

[233] Ruan X, Yan W, Cao M, et al. Breast cancer cell-secreted miR-199b-5p hijacks neurometabolic coupling to promote brain metastasis. Nat Commun. 2024; 15(1): 4549.

[234] Ozer O, Nemutlu E, Recber T, et al. Liquid biopsy markers for early diagnosis of brain metastasis patients with breast cancer by metabolomics. Eur J Mass Spectrom (Chichester). 2022; 28(1-2): 56-64.

[235] Parida PK, Marquez-Palencia M, Nair V, et al. Metabolic diversity within breast cancer brain-tropic cells determines metastatic fitness. Cell Metab. 2022; 34(1): 90-105. e7.

[236] Ferraro GB, Ali A, Luengo A, et al. Fatty acid synthesis is required for breast cancer brain metastasis. Nat Cancer. 2021; 2(4): 414-428.

[237] Xiao H, Vaidya R, Hershman DL, Unger JM. Impact of broadening trial eligibility criteria on the inclusion of patients with brain metastases in cancer clinical trials: time series analyses for 2012–2022. J Clin Oncol. 2024; 42(16): 1953-1960.

[238] Vogelbaum MA, Brown PD, Messersmith H, et al. Treatment for brain metastases: ASCO-SNO-ASTRO guideline. J Clin Oncol. 2022; 40(5): 492-516.

[239] LeSavage BL, Suhar RA, Broguiere N, Lutolf MP, Heilshorn SC. Next-generation cancer organoids. Nat Mater. 2022; 21(2): 143-159.

[240] Qian X, Song H, Ming GL. Brain organoids: advances, applications and challenges. Development. 2019; 146(8): dev166074.

[241] Li W, Zhou Z, Zhou X, et al. 3D biomimetic models to reconstitute tumor microenvironment in vitro: spheroids, organoids, and tumor-on-a-chip. Adv Healthc Mater. 2023; 12(18): e2202609.

[242] Godinho-Pereira J, Vaz D, Figueira I, et al. Breast cancer brain metastases: implementation and characterization of a mouse model relying on malignant cells inoculation in the carotid artery. Cells. 2023; 12(16): 2076.

[243] Munsterberg J, Loreth D, Brylka L, et al. ALCAM contributes to brain metastasis formation in non-small-cell lung cancer through interaction with the vascular endothelium. Neuro Oncol. 2020; 22(7): 955-966.

[244] Qu F, Brough SC, Michno W, et al. Crosstalk between small-cell lung cancer cells and astrocytes mimics brain development to promote brain metastasis. Nat Cell Biol. 2023; 25(10): 1506-1519.

[245] Valiente M, Van Swearingen AED, Anders CK, et al. Brain metastasis cell lines panel: a public resource of organotropic cell lines. Cancer Res. 2020; 80(20): 4314-4323.

[246] Fan RY, Wu JQ, Liu YY, et al. Zebrafish xenograft model for studying mechanism and treatment of non-small cell lung cancer brain metastasis. J Exp Clin Cancer Res. 2021; 40(1): 371.

[247] Zhang SR, Pan M, Gao YB, et al. Efficacy and mechanism study of cordycepin against brain metastases of small cell lung cancer based on zebrafish. Phytomedicine. 2023; 109: 154613.

[248] Shi W, Tanzhu G, Chen L, et al. Radiotherapy in preclinical models of brain metastases: a review and recommendations for future studies. Int J Biol Sci. 2024; 20(2): 765-783.

[249] Liu X, Liu S, Yang Y, et al. Animal models of brain and spinal cord metastases of NSCLC established using a brain stereotactic instrument. Heliyon. 2024; 10(3): e24809.

[250] Huang L, Wan J, Wu Y, et al. Challenges in adeno-associated virus-based treatment of central nervous system diseases through systemic injection. Life Sci. 2021; 270: 119142.

[251] Wyss CB, Duffey N, Peyvandi S, et al. Gain of HIF1 activity and loss of miRNA let-7d promote breast cancer metastasis to the brain via the PDGF/PDGFR axis. Cancer Res. 2021; 81(3): 594-605.

[252] Huo KG, D’Arcangelo E, Tsao MS. Patient-derived cell line, xenograft and organoid models in lung cancer therapy. Transl Lung Cancer Res. 2020; 9(5): 2214-2232.

[253] Liu Y, Wu W, Cai C, Zhang H, Shen H, Han Y. Patient-derived xenograft models in cancer therapy: technologies and applications. Signal Transduct Target Ther. 2023; 8(1): 160.

[254] Evans KT, Blake K, Longworth A, et al. Microglia promote anti-tumour immunity and suppress breast cancer brain metastasis. Nat Cell Biol. 2023; 25(12): 1848-1859.

[255] Contreras-Zarate MJ, Alvarez-Eraso KLF, Jaramillo-Gomez JA, et al. Short-term topiramate treatment prevents radiation-induced cytotoxic edema in preclinical models of breast-cancer brain metastasis. Neuro Oncol. 2023; 25(10): 1802-1814.

[256] Kretzschmar K. Cancer research using organoid technology. J Mol Med (Berl). 2021; 99(4): 501-515.

[257] Drexler R, Khatri R, Sauvigny T, et al. A prognostic neural epigenetic signature in high-grade glioma. Nat Med. 2024; 30(6): 1622-1635.

[258] Bian S, Repic M, Guo Z, et al. Genetically engineered cerebral organoids model brain tumor formation. Nat Methods. 2018; 15(8): 631-639.

[259] Hendriks D, Pagliaro A, Andreatta F, et al. Human fetal brain self-organizes into long-term expanding organoids. Cell. 2024; 187(3): 712-732. e38.

[260] Huang M, Xu S, Li Y, et al. Novel human meningioma organoids recapitulate the aggressiveness of the initiating cell subpopulations identified by ScRNA-Seq. Adv Sci (Weinh). 2023; 10(15): e2205525.

[261] Fitzpatrick A, Iravani M, Mills A, et al. Genomic profiling and pre-clinical modelling of breast cancer leptomeningeal metastasis reveals acquisition of a lobular-like phenotype. Nat Commun. 2023; 14(1): 7408.

[262] Choe MS, Kim JS, Yeo HC, et al. A simple metastatic brain cancer model using human embryonic stem cell-derived cerebral organoids. FASEB J. 2020; 34(12): 16464-16475.

[263] Quaranta V, Linkous A. Organoids as a systems platform for SCLC brain metastasis. Front Oncol. 2022; 12: 881989.

[264] Li H, Harrison EB, Li H, et al. Targeting brain lesions of non-small cell lung cancer by enhancing CCL2-mediated CAR-T cell migration. Nat Commun. 2022; 13(1): 2154.

[265] Krieger TG, Tirier SM, Park J, et al. Modeling glioblastoma invasion using human brain organoids and single-cell transcriptomics. Neuro Oncol. 2020; 22(8): 1138-1149.

[266] Wang X, Liang H, Tang X, Ling X, Yang Y. Single-cell RNA sequencing reveals distinct transcriptomic profiles and evolutionary patterns in lung cancer brain metastasis. Heliyon. 2024; 10(5): e27071.

[267] Zhu L, Retana D, Garcia-Gomez P, et al. A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis. EMBO Mol Med. 2022; 14(3): e14552.

[268] Wang J, Meng X, Yu M, et al. A novel microfluidic system for enrichment of functional circulating tumor cells in cancer patient blood samples by combining cell size and invasiveness. Biosens Bioelectron. 2023; 227: 115159.

[269] Liu W, Song J, Du X, et al. AKR1B10 (Aldo-keto reductase family 1 B10) promotes brain metastasis of lung cancer cells in a multi-organ microfluidic chip model. Acta Biomater. 2019; 91: 195-208.

[270] Xu M, Wang Y, Duan W, et al. Proteomic reveals reasons for acquired drug resistance in lung cancer derived brain metastasis based on a newly established multi-organ microfluidic chip model. Front Bioeng Biotechnol. 2020; 8: 612091.

[271] Kim H, Sa JK, Kim J, et al. Recapitulated Crosstalk between cerebral metastatic lung cancer cells and brain perivascular tumor microenvironment in a microfluidic co-culture chip. Adv Sci (Weinh). 2022; 9(22): e2201785.

[272] Xia S, Duan W, Xu M, et al. Mesothelin promotes brain metastasis of non-small cell lung cancer by activating MET. J Exp Clin Cancer Res. 2024; 43(1): 103.

[273] Loreth D, Schuette M, Zinke J, et al. CD74 and CD44 expression on CTCs in cancer patients with brain metastasis. Int J Mol Sci. 2021; 22(13): 6993.

[274] Wang Z, Zhang Y, Li Z, Wang H, Li N, Deng Y. Microfluidic brain-on-a-chip: from key technology to system integration and application. Small. 2023; 19(52): e2304427.

[275] Sood A, Kumar A, Dev A, Gupta VK, Han SS. Advances in hydrogel-based microfluidic blood-brain-barrier models in oncology research. Pharmaceutics. 2022; 14(5): 993.

[276] Lim J, Rhee S, Choi H, et al. Engineering choroid plexus-on-a-chip with oscillatory flow for modeling brain metastasis. Mater Today Bio. 2023; 22: 100773.

[277] Turker E, Andrade Mier MS, Faber J, et al. Breast tumor cell survival and morphology in a brain-like extracellular matrix depends on matrix composition and mechanical properties. Adv Biol (Weinh). 2024; 8: e2400184.

[278] Augustine R, Zahid AA, Mraiche F, Alam K, Al Moustafa AE, Hasan A. Gelatin-methacryloyl hydrogel based in vitro blood-brain barrier model for studying breast cancer-associated brain metastasis. Pharm Dev Technol. 2021; 26(4): 490-500.

[279] Narkhede AA, Crenshaw JH, Crossman DK, Shevde LA, Rao SS. An in vitro hyaluronic acid hydrogel based platform to model dormancy in brain metastatic breast cancer cells. Acta Biomater. 2020; 107: 65-77.

[280] Goodarzi K, Lane R, Rao SS. Varying the RGD concentration on a hyaluronic acid hydrogel influences dormancy versus proliferation in brain metastatic breast cancer cells. J Biomed Mater Res A. 2024; 112(5): 710-720.

[281] Kondapaneni RV, Shevde LA, Rao SS. A biomimetic hyaluronic acid hydrogel models mass dormancy in brain metastatic breast cancer spheroids. Adv Biol (Weinh). 2023; 7(1): e2200114.

[282] Yakati V, Shevde LA, Rao SS. Matrix stiffness influences response to chemo and targeted therapy in brain metastatic breast cancer cells. Biomater Sci. 2024; 12(15): 3882-3895.

[283] Li J, Jiang J, Bao X, et al. Mechanistic modeling of central nervous system pharmacokinetics and target engagement of HER2 tyrosine kinase inhibitors to inform treatment of breast cancer brain metastases. Clin Cancer Res. 2022; 28(15): 3329-3341.

[284] Zu L, He J, Zhou N, Tang Q, Liang M, Xu S. Identification of multiple organ metastasis-associated hub mRNA/miRNA signatures in non-small cell lung cancer. Cell Death Dis. 2023; 14(12): 798.

[285] Chen Q, Pan Q, Gao H, Wang Y, Zhong X. miR-17-5p/HOXA7 is a potential driver for brain metastasis of lung adenocarcinoma related to ferroptosis revealed by bioinformatic analysis. Front Neurol. 2022; 13: 878947.

[286] Roskova I, Vecera M, Radova L, et al. Small RNA sequencing identifies a six-microRNA signature enabling classification of brain metastases according to their origin. Cancer Genomics Proteomics. 2023; 20(1): 18-29.

[287] Karimpour M, Ravanbakhsh R, Maydanchi M, Rajabi A, Azizi F, Saber A. Cancer driver gene and non-coding RNA alterations as biomarkers of brain metastasis in lung cancer: a review of the literature. Biomed Pharmacother. 2021; 143: 112190.

[288] Zhang XQ, Song Q, Zeng LX. Circulating hsa_circ_0072309, acting via the miR-100/ACKR3 pathway, maybe a potential biomarker for the diagnosis, prognosis, and treatment of brain metastasis from non-small-cell lung cancer. Cancer Med. 2023; 12(17): 18005-18019.

[289] Song Z, Yang L, Zhou Z, et al. Genomic profiles and tumor immune microenvironment of primary lung carcinoma and brain oligo-metastasis. Cell Death Dis. 2021; 12(1): 106.

[290] Liu JS, Cai YX, He YZ, Xu J, Tian SF, Li ZQ. Spatial and temporal heterogeneity of tumor immune microenvironment between primary tumor and brain metastases in NSCLC. BMC Cancer. 2024; 24(1): 123.

[291] Song SG, Kim S, Koh J, et al. Comparative analysis of the tumor immune-microenvironment of primary and brain metastases of non-small-cell lung cancer reveals organ-specific and EGFR mutation-dependent unique immune landscape. Cancer Immunol Immunother. 2021; 70(7): 2035-2048.

[292] Li M, Hou X, Sai K, et al. Immune suppressive microenvironment in brain metastatic non-small cell lung cancer: comprehensive immune microenvironment profiling of brain metastases versus paired primary lung tumors (GASTO 1060). Oncoimmunology. 2022; 11(1): 2059874.

[293] Vilarino N, Bruna J, Bosch-Barrera J, Valiente M, Nadal E. Immunotherapy in NSCLC patients with brain metastases. Understanding brain tumor microenvironment and dissecting outcomes from immune checkpoint blockade in the clinic. Cancer Treat Rev. 2020; 89: 102067.

[294] Tsakonas G, Koulouris A, Kazmierczak D, et al. Matched analyses of brain metastases versus primary non-small cell lung cancer reveal a unique microRNA signature. Int J Mol Sci. 2022; 24(1): 193.

[295] Xiao L, Zhou J, Liu H, et al. RNA sequence profiling reveals unique immune and metabolic features of breast cancer brain metastases. Front Oncol. 2021; 11: 679262.

[296] Joshi V, Beecher K, Lim M, et al. B7-H3 expression in breast cancer and brain metastasis. Int J Mol Sci. 2024; 25(7): 3976.

[297] Zhang Z, Cui F, Zhou M, Wu S, Zou Q, Gao B. Single-cell RNA sequencing analysis identifies key genes in brain metastasis from lung adenocarcinoma. Curr Gene Ther. 2021; 21(4): 338-348.

[298] Jovic D, Liang X, Zeng H, Lin L, Xu F, Luo Y. Single-cell RNA sequencing technologies and applications: A brief overview. Clin Transl Med. 2022; 12(3): e694.

[299] Van de Sande B, Lee JS, Mutasa-Gottgens E, et al. Applications of single-cell RNA sequencing in drug discovery and development. Nat Rev Drug Discov. 2023; 22(6): 496-520.

[300] Chen M, Li H, Xu X, et al. Identification of RAC1 in promoting brain metastasis of lung adenocarcinoma using single-cell transcriptome sequencing. Cell Death Dis. 2023; 14(5): 330.

[301] Liang J, Liang R, Lei K, Huang J, Lin H, Wang M. Comparative analysis of single-cell transcriptome reveals heterogeneity in the tumor microenvironment of lung adenocarcinoma and brain metastases. Discov Oncol. 2023; 14(1): 174.

[302] Wu Y, Yang F, Luo S, et al. Single-cell RNA sequencing reveals epithelial cells driving brain metastasis in lung adenocarcinoma. iScience. 2024; 27(3): 109258.

[303] Xie J, Yang A, Liu Q, et al. Single-cell RNA sequencing elucidated the landscape of breast cancer brain metastases and identified ILF2 as a potential therapeutic target. Cell Prolif. 2024; 57: e13697.

[304] Zou Y, Ye F, Kong Y, et al. The single-cell landscape of intratumoral heterogeneity and the immunosuppressive microenvironment in liver and brain metastases of breast cancer. Adv Sci (Weinh). 2023; 10(5): e2203699.

[305] Bejarano L, Kauzlaric A, Lamprou E, et al. Interrogation of endothelial and mural cells in brain metastasis reveals key immune-regulatory mechanisms. Cancer Cell. 2024; 42(3): 378-395. e10.

[306] Zormpas E, Queen R, Comber A, Cockell SJ. Mapping the transcriptome: realizing the full potential of spatial data analysis. Cell. 2023; 186(26): 5677-5689.

[307] Karimi E, Yu MW, Maritan SM, et al. Single-cell spatial immune landscapes of primary and metastatic brain tumours. Nature. 2023; 614(7948): 555-563.

[308] Wang D, Liu B, Zhang Z. Accelerating the understanding of cancer biology through the lens of genomics. Cell. 2023; 186(8): 1755-1771.

[309] Nguyen B, Fong C, Luthra A, et al. Genomic characterization of metastatic patterns from prospective clinical sequencing of 25, 000 patients. Cell. 2022; 185(3): 563-575. e11.

[310] Huang RSP, Harries L, Decker B, et al. Clinicopathologic and genomic landscape of non-small cell lung cancer brain metastases. Oncologist. 2022; 27(10): 839-848.

[311] Smyth EN, John J, Tiu RV, et al. Clinicogenomic factors and treatment patterns among patients with advanced non-small cell lung cancer with or without brain metastases in the United States. Oncologist. 2023; 28(11): e1075-e1091.

[312] Chan KH, Sridhar A, Lin JZ, Jafri SHR. Genomic profiling and sites of metastasis in non-small cell lung cancer. Front Oncol. 2023; 13: 1212788.

[313] Sivakumar S, Moore JA, Montesion M, et al. Integrative analysis of a large real-world cohort of small cell lung cancer identifies distinct genetic subtypes and insights into histologic transformation. Cancer Discov. 2023; 13(7): 1572-1591.

[314] Wardell CP, Darrigues E, De Loose A, et al. Genomic and transcriptomic profiling of brain metastases. Cancers (Basel). 2021; 13(22): 5598.

[315] Skakodub A, Walch H, Tringale KR, et al. Genomic analysis and clinical correlations of non-small cell lung cancer brain metastasis. Nat Commun. 2023; 14(1): 4980.

[316] Wang X, Bai H, Zhang J, et al. Genetic intratumor heterogeneity remodels the immune microenvironment and induces immune evasion in brain metastasis of lung cancer. J Thorac Oncol. 2024; 19(2): 252-272.

[317] Xie T, Liu Z, Li Y, et al. Evolutionary characteristics and immunologic divergence of lung and brain metastasis lesions in NSCLC. Mol Cancer Res. 2023; 21(4): 374-385.

[318] Chen J, Yang H, Zhao C, et al. Mutational signatures of synchronous and metachronous brain metastases from lung adenocarcinoma. Exp Hematol Oncol. 2023; 12(1): 54.

[319] Deng Z, Cui L, Li P, et al. Genomic comparison between cerebrospinal fluid and primary tumor revealed the genetic events associated with brain metastasis in lung adenocarcinoma. Cell Death Dis. 2021; 12(10): 935.

[320] Giannoudis A, Sartori A, Eastoe L, et al. Genomic profiling using the UltraSEEK panel identifies discordancy between paired primary and breast cancer brain metastases and an association with brain metastasis-free survival. Breast Cancer Res Treat. 2021; 190(2): 241-253.

[321] Morgan AJ, Giannoudis A, Palmieri C. The genomic landscape of breast cancer brain metastases: a systematic review. Lancet Oncol. 2021; 22(1): e7-e17.

[322] Thulin A, Andersson C, Werner Ronnerman E, et al. Discordance of PIK3CA and TP53 mutations between breast cancer brain metastases and matched primary tumors. Sci Rep. 2021; 11(1): 23548.

[323] Dono A, Takayasu T, Yan Y, et al. Differences in genomic alterations between brain metastases and primary tumors. Neurosurgery. 2021; 88(3): 592-602.

[324] Bhogal T, Giannoudis A, Sokol E, Ali S, Palmieri C. Analysis of breast cancer brain metastases reveals an enrichment of cyclin-dependent kinase 12 structural rearrangements in human epidermal growth factor receptor 2-positive disease. JCO Precis Oncol. 2024; 8: e2300639.

[325] Lu Q, Wang N, Jiang K, et al. Comprehensive genomic profiling to identify actionable alterations for breast cancer brain metastases in the Chinese population. ESMO Open. 2024; 9(3): 102389.

[326] Huang RSP, Haberberger J, McGregor K, et al. Clinicopathologic and genomic landscape of breast carcinoma brain metastases. Oncologist. 2021; 26(10): 835-844.

[327] Nguyen TT, Hamdan D, Angeli E, et al. Genomics of breast cancer brain metastases: a meta-analysis and therapeutic implications. Cancers (Basel). 2023; 15(6): 1728.

[328] Barakeh DH, Alsolme E, Alqubaishi F, et al. Clinicopathologic and genomic characterizations of brain metastases using a comprehensive genomic panel. Front Med (Lausanne). 2022; 9: 947456.

[329] Cosgrove N, Vareslija D, Keelan S, et al. Mapping molecular subtype specific alterations in breast cancer brain metastases identifies clinically relevant vulnerabilities. Nat Commun. 2022; 13(1): 514.

[330] Tew BY, Kalfa AJ, Yang Z, et al. ATM-inhibitor AZD1390 is a radiosensitizer for breast cancer CNS metastasis. Clin Cancer Res. 2023; 29(21): 4492-4503.

[331] Parida PK, Marquez-Palencia M, Ghosh S, et al. Limiting mitochondrial plasticity by targeting DRP1 induces metabolic reprogramming and reduces breast cancer brain metastases. Nat Cancer. 2023; 4(6): 893-907.

[332] Najjary S, de Koning W, Kros JM, Mustafa DAM. Unlocking molecular mechanisms and identifying druggable targets in matched-paired brain metastasis of breast and lung cancers. Front Immunol. 2023; 14: 1305644.

[333] Levallet J, Biojout T, Bazille C, et al. Hypoxia-induced activation of NDR2 underlies brain metastases from non-small cell lung cancer. Cell Death Dis. 2023; 14(12): 823.

[334] Kalita B, Coumar MS. Deciphering breast cancer metastasis cascade: a systems biology approach integrating transcriptome and interactome insights for target discovery. OMICS. 2024; 28(3): 148-161.

[335] Alvarez-Prado AF, Maas RR, Soukup K, et al. Immunogenomic analysis of human brain metastases reveals diverse immune landscapes across genetically distinct tumors. Cell Rep Med. 2023; 4(1): 100900.

[336] Li S, Qu Y, Liu L, et al. Comparative proteomic profiling of plasma exosomes in lung cancer cases of liver and brain metastasis. Cell Biosci. 2023; 13(1): 180.

[337] Deng Q, Wang F, Song L, et al. Proteomics-based model for predicting the risk of brain metastasis in patients with resected lung adenocarcinoma carrying the EGFR mutation. Int J Med Sci. 2024; 21(4): 765-774.

[338] Fantin J, Toutain J, Peres EA, et al. Assessment of hypoxia and oxidative-related changes in a lung-derived brain metastasis model by [(64)Cu][Cu(ATSM)] PET and proteomic studies. EJNMMI Res. 2023; 13(1): 102.

[339] Wei S, Liu W, Xu M, et al. Cathepsin F and Fibulin-1 as novel diagnostic biomarkers for brain metastasis of non-small cell lung cancer. Br J Cancer. 2022; 126(12): 1795-1805.

[340] Zhao Y, Gu S, Li L, et al. A novel risk signature for predicting brain metastasis in patients with lung adenocarcinoma. Neuro Oncol. 2023; 25(12): 2207-2220.

[341] Wu AML, Gossa S, Samala R, et al. Aging and CNS myeloid cell depletion attenuate breast cancer brain metastasis. Clin Cancer Res. 2021; 27(15): 4422-4434.

[342] Hunt AL, Khan I, Wu AML, et al. The murine metastatic microenvironment of experimental brain metastases of breast cancer differs by host age in vivo: a proteomic study. Clin Exp Metastasis. 2024; 41(3): 229-249.

[343] Maurya SK, Rehman AU, Zaidi MAA, et al. Epigenetic alterations fuel brain metastasis via regulating inflammatory cascade. Semin Cell Dev Biol. 2024; 154(Pt C): 261-274.

[344] Karlow JA, Devarakonda S, Xing X, et al. Developmental pathways are epigenetically reprogrammed during lung cancer brain metastasis. Cancer Res. 2022; 82(15): 2692-2703.

[345] Xu Y, Huang Z, Yu X, Chen K, Fan Y. Integrated genomic and DNA methylation analysis of patients with advanced non-small cell lung cancer with brain metastases. Mol Brain. 2021; 14(1): 176.

[346] Pangeni RP, Olivaries I, Huen D, et al. Genome-wide methylation analyses identifies non-coding RNA genes dysregulated in breast tumours that metastasise to the brain. Sci Rep. 2022; 12(1): 1102.

[347] Ning J, Chen L, Xiao G, et al. The protein arginine methyltransferase family (PRMTs) regulates metastases in various tumors: from experimental study to clinical application. Biomed Pharmacother. 2023; 167: 115456.

[348] Li Y, Cao J, Wang J, Wu W, Jiang L, Sun X. Association of the m(6) A reader IGF2BP3 with tumor progression and brain-specific metastasis in breast cancer. Cancer. 2024; 130(3): 356-374.

[349] Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov. 2022; 12(1): 31-46.

[350] Agirman G, Yu KB, Hsiao EY. Signaling inflammation across the gut-brain axis. Science. 2021; 374(6571): 1087-1092.

[351] Lin B, Ye Z, Ye Z, et al. Gut microbiota in brain tumors: An emerging crucial player. CNS Neurosci Ther. 2023; 29(Suppl 1): 84-97.

[352] Lu H, Gao NL, Tong F, et al. Alterations of the human lung and gut microbiomes in non-small cell lung carcinomas and distant metastasis. Microbiol Spectr. 2021; 9(3): e0080221.

[353] Jiang H, Zeng W, Zhang X, et al. Gut microbiota and its metabolites in non-small cell lung cancer and brain metastasis: from alteration to potential microbial markers and drug targets. Front Cell Infect Microbiol. 2023; 13: 1211855.

[354] Copoiu L, Malhotra S. The current structural glycome landscape and emerging technologies. Curr Opin Struct Biol. 2020; 62: 132-139.

[355] Onigbinde S, Peng W, Reddy A, et al. O-glycome profiling of breast cancer cell lines to understand breast cancer brain metastasis. J Proteome Res. 2024; 23(4): 1458-1470.

[356] Souza VGP, Telkar N, Lam WL, Reis PP. Comprehensive analysis of lung adenocarcinoma and brain metastasis through integrated single-cell transcriptomics. Int J Mol Sci. 2024; 25(7): 3779.

[357] Fukumura K, Malgulwar PB, Fischer GM, et al. Multi-omic molecular profiling reveals potentially targetable abnormalities shared across multiple histologies of brain metastasis. Acta Neuropathol. 2021; 141(2): 303-321.

[358] Klemm F, Maas RR, Bowman RL, et al. Interrogation of the microenvironmental landscape in brain tumors reveals disease-specific alterations of immune cells. Cell. 2020; 181(7): 1643-1660. e17.

[359] Lin YY, Wang YC, Yeh DW, et al. Gene expression profile in primary tumor is associated with brain-tropism of metastasis from lung adenocarcinoma. Int J Mol Sci. 2021; 22(24): 13374.

[360] Chen J, Hu C, Yang H, et al. PMS2 amplification contributes brain metastasis from lung cancer. Biol Proced Online. 2024; 26(1): 12.

[361] Xu Y, Pan J, Lin Y, Wu Y, Chen Y, Li H. Ceramide synthase 1 inhibits brain metastasis of non-small cell lung cancer by interacting with USP14 and downregulating the PI3K/AKT/mTOR signaling pathway. Cancers (Basel). 2023; 15(7): 1994.

[362] Chaudhary S, Siddiqui JA, Appadurai MI, et al. Dissecting the MUC5AC/ANXA2 signaling axis: implications for brain metastasis in lung adenocarcinoma. Exp Mol Med. 2024; 56(6): 1450-146.

[363] Fang H, Sun Q, Zhou J, et al. m(6)A methylation reader IGF2BP2 activates endothelial cells to promote angiogenesis and metastasis of lung adenocarcinoma. Mol Cancer. 2023; 22(1): 99.

[364] Li H, Tong F, Meng R, et al. E2F1-mediated repression of WNT5A expression promotes brain metastasis dependent on the ERK1/2 pathway in EGFR-mutant non-small cell lung cancer. Cell Mol Life Sci. 2021; 78(6): 2877-2891.

[365] Zhong J, Wang B. Long noncoding RNA LGALS8-AS1 promotes angiogenesis and brain metastases in non-small cell lung cancer. Acta Biochim Pol. 2023; 70(3): 551-559.

[366] Margarido AS, Uceda-Castro R, Hahn K, et al. Epithelial-to-mesenchymal transition drives invasiveness of breast cancer brain metastases. Cancers (Basel). 2022; 14(13): 3115.

[367] Sahu SK, Agirre E, Inayatullah M, et al. A complex epigenome-splicing crosstalk governs epithelial-to-mesenchymal transition in metastasis and brain development. Nat Cell Biol. 2022; 24(8): 1265-1277.

[368] Zhang L, Wang L, Yang H, Li C, Fang C. Identification of potential genes related to breast cancer brain metastasis in breast cancer patients. Biosci Rep. 2021; 41(10): BSR20211615.

[369] Hamester F, Sturken C, Legler K, et al. Key role of hyaluronan metabolism for the development of brain metastases in triple-negative breast cancer. Cells. 2022; 11(20): 3275.

[370] Zhao Y, Tang X, Lei T, Fu D, Zhang H. Lipocalin-2 promotes breast cancer brain metastasis by enhancing tumor invasion and modulating brain microenvironment. Front Oncol. 2024; 14: 1448089.

[371] Seehawer M, Li Z, Nishida J, et al. Loss of Kmt2c or Kmt2d drives brain metastasis via KDM6A-dependent upregulation of MMP3. Nat Cell Biol. 2024; 26(7): 1165-1175.

[372] Fu B, Liu W, Zhu C, et al. Circular RNA circBCBM1 promotes breast cancer brain metastasis by modulating miR-125a/BRD4 axis. Int J Biol Sci. 2021; 17(12): 3104-3117.

[373] Khoshbakht S, Zomorodi Anbaji F, Darzi M, Esmaeili R. The endogenous association among MMP2/miR-1248/Circ_0087558/miR-643/MAP2K6 axis can contribute to brain metastasis in basal-like subtype of breast cancer. Heliyon. 2024; 10(13): e33195.

[374] Ning J, Luo Y, Chen L, Xiao G, Tanzhu G, Zhou R. CircRNAs and lung cancer: insight into their roles in metastasis. Biomed Pharmacother. 2023; 166: 115260.

[375] Wu C, Weis SM, Cheresh DA. Tumor-initiating cells establish a niche to overcome isolation stress. Trends Cell Biol. 2024; 34(5): 380-387.

[376] Bassey-Archibong BI, Rajendra Chokshi C, Aghaei N, et al. An HLA-G/SPAG9/STAT3 axis promotes brain metastases. Proc Natl Acad Sci USA. 2023; 120(8): e2205247120.

[377] Huang Q, Liu L, Xiao D, et al. CD44(+) lung cancer stem cell-derived pericyte-like cells cause brain metastases through GPR124-enhanced trans-endothelial migration. Cancer Cell. 2023; 41(9): 1621-1636. e8.

[378] Tyagi A, Wu SY, Sharma S, et al. Exosomal miR-4466 from nicotine-activated neutrophils promotes tumor cell stemness and metabolism in lung cancer metastasis. Oncogene. 2022; 41(22): 3079-3092.

[379] Berghoff AS, Liao Y, Karreman MA, et al. Identification and characterization of cancer cells that initiate metastases to the brain and other organs. Mol Cancer Res. 2021; 19(4): 688-701.

[380] Deasy SK, Erez N. A glitch in the matrix: organ-specific matrisomes in metastatic niches. Trends Cell Biol. 2022; 32(2): 110-123.

[381] Wang L, Li C, Zhan H, et al. Targeting the HSP47-collagen axis inhibits brain metastasis by reversing M2 microglial polarization and restoring anti-tumor immunity. Cell Rep Med. 2024; 5(5): 101533.

[382] Zhao C, Zhang Z, Hu X, et al. Hyaluronic acid correlates with bone metastasis and predicts poor prognosis in small-cell lung cancer patients. Front Endocrinol (Lausanne). 2021; 12: 785192.

[383] You M, Fu M, Shen Z, et al. HIF2A mediates lineage transition to aggressive phenotype of cancer-associated fibroblasts in lung cancer brain metastasis. Oncoimmunology. 2024; 13(1): 2356942.

[384] Souza VGP, de Araujo RP, Santesso MR, et al. Advances in the molecular landscape of lung cancer brain metastasis. Cancers (Basel). 2023; 15(3): 722.

[385] Rehman AU, Khan P, Maurya SK, et al. Liquid biopsies to occult brain metastasis. Mol Cancer. 2022; 21(1): 113.

[386] Klotz R, Thomas A, Teng T, et al. Circulating tumor cells exhibit metastatic tropism and reveal brain metastasis drivers. Cancer Discov. 2020; 10(1): 86-103.

[387] Wang L, Liu W, Liu K, et al. The dynamic dysregulated network identifies stage-specific markers during lung adenocarcinoma malignant progression and metastasis. Mol Ther Nucleic Acids. 2022; 30: 633-647.

[388] Alsabbagh R, Ahmed M, Alqudah MAY, Hamoudi R, Harati R. Insights into the molecular mechanisms mediating extravasation in brain metastasis of breast cancer, melanoma, and lung cancer. Cancers (Basel). 2023; 15(8): 2258.

[389] Bao X, Wu J, Jiang J, Tien AC, Sanai N, Li J. Quantitative protein expression of blood-brain barrier transporters in the vasculature of brain metastases of patients with lung and breast cancer. Clin Transl Sci. 2021; 14(4): 1265-1271.

[390] Schaffenrath J, Wyss T, He L, et al. Blood-brain barrier alterations in human brain tumors revealed by genome-wide transcriptomic profiling. Neuro Oncol. 2021; 23(12): 2095-2106.

[391] Zhu L, Yang F, Wang G, Li Q. CXC motif chemokine receptor type 4 disrupts blood-brain barrier and promotes brain metastasis through activation of the PI3K/AKT pathway in lung cancer. World Neurosurg. 2022; 166: e369-e381.

[392] Wu D, Deng S, Li L, et al. TGF-beta1-mediated exosomal lnc-MMP2-2 increases blood-brain barrier permeability via the miRNA-1207-5p/EPB41L5 axis to promote non-small cell lung cancer brain metastasis. Cell Death Dis. 2021; 12(8): 721.

[393] Geng S, Tu S, Bai Z, Geng Y. Exosomal lncRNA LINC01356 derived from brain metastatic nonsmall-cell lung cancer cells remodels the blood-brain barrier. Front Oncol. 2022; 12: 825899.

[394] Mao S, Zheng S, Lu Z, et al. Exosomal miR-375-3p breaks vascular barrier and promotes small cell lung cancer metastasis by targeting claudin-1. Transl Lung Cancer Res. 2021; 10(7): 3155-3172.

[395] Ahmad A, Khan P, Rehman AU, Batra SK, Nasser MW. Immunotherapy: an emerging modality to checkmate brain metastasis. Mol Cancer. 2023; 22(1): 111.

[396] Gonzalez H, Mei W, Robles I, et al. Cellular architecture of human brain metastases. Cell. 2022; 185(4): 729-745. e20.

[397] Lah TT, Novak M, Breznik B. Brain malignancies: glioblastoma and brain metastases. Semin Cancer Biol. 2020; 60: 262-273.

[398] Arvanitis CD, Ferraro GB, Jain RK. The blood-brain barrier and blood-tumour barrier in brain tumours and metastases. Nat Rev Cancer. 2020; 20(1): 26-41.

[399] Zhou D, Gong Z, Wu D, et al. Harnessing immunotherapy for brain metastases: insights into tumor-brain microenvironment interactions and emerging treatment modalities. J Hematol Oncol. 2023; 16(1): 121.

[400] Dankner M, Maritan SM, Priego N, et al. Invasive growth of brain metastases is linked to CHI3L1 release from pSTAT3-positive astrocytes. Neuro Oncol. 2024; 26(6): 1052-1066.

[401] Tang M, Xu M, Wang J, et al. Brain metastasis from EGFR-mutated non-small cell lung cancer: secretion of IL11 from astrocytes up-regulates PDL1 and promotes immune escape. Adv Sci (Weinh). 2024:e2306348.

[402] Feng Y, Hu X, Zhang Y, Wang Y. The role of microglia in brain metastases: mechanisms and strategies. Aging Dis. 2024; 15(1): 169-185.

[403] Chen S, Liu YJ. Microglia suppresses breast cancer brain metastasis via a pro-inflammatory response. Neurosci Bull. 2024;

[404] Liu L, Wang J, Wang Y, et al. Blocking the MIF-CD74 axis augments radiotherapy efficacy for brain metastasis in NSCLC via synergistically promoting microglia M1 polarization. J Exp Clin Cancer Res. 2024; 43(1): 128.

[405] Jin Y, Kang Y, Wang M, et al. Targeting polarized phenotype of microglia via IL6/JAK2/STAT3 signaling to reduce NSCLC brain metastasis. Signal Transduct Target Ther. 2022; 7(1): 52.

[406] She X, Shen S, Chen G, et al. Immune surveillance of brain metastatic cancer cells is mediated by IFITM1. EMBO J. 2023; 42(7): e111112.

[407] Xu W, Patel N, Deng Y, Ding S, Wang T, Zhang H. Extracellular vesicle-derived LINC00482 induces microglial M2 polarization to facilitate brain metastasis of NSCLC. Cancer Lett. 2023; 561: 216146.

[408] Economopoulos V, Pannell M, Johanssen VA, et al. Inhibition of anti-inflammatory macrophage phenotype reduces tumour growth in mouse models of brain metastasis. Front Oncol. 2022; 12: 850656.

[409] Kim HJ, Park JH, Kim HC, Kim CW, Kang I, Lee HK. Blood monocyte-derived CD169(+) macrophages contribute to antitumor immunity against glioblastoma. Nat Commun. 2022; 13(1): 6211.

[410] Wang W, Li T, Cheng Y, et al. Identification of hypoxic macrophages in glioblastoma with therapeutic potential for vasculature normalization. Cancer Cell. 2024; 42(5): 815-832. e12.

[411] Khan F, Pang L, Dunterman M, Lesniak MS, Heimberger AB, Chen P. Macrophages and microglia in glioblastoma: heterogeneity, plasticity, and therapy. J Clin Invest. 2023; 133(1): e163446.

[412] Kleffman K, Levinson G, Rose IVL, et al. Melanoma-secreted amyloid beta suppresses neuroinflammation and promotes brain metastasis. Cancer Discov. 2022; 12(5): 1314-1335.

[413] DeCastro AJL, Pranda MA, Gray KM, et al. Morphological phenotyping of organotropic brain-and bone-seeking triple negative metastatic breast tumor cells. Front Cell Dev Biol. 2022; 10: 790410.

[414] Zhang B, Li X, Tang K, et al. Adhesion to the brain endothelium selects breast cancer cells with brain metastasis potential. Int J Mol Sci. 2023; 24(8): 7087.

[415] Jagust P, Powell AM, Ola M, et al. RET overexpression leads to increased brain metastatic competency in luminal breast cancer. J Natl Cancer Inst. 2024; 116(10): 1632-1644.

[416] Pan JK, Lin WD, Kuo YL, et al. ICAM2 initiates trans-blood-CSF barrier migration and stemness properties in leptomeningeal metastasis of triple-negative breast cancer. Oncogene. 2023; 42(39): 2919-2931.

[417] Fazakas C, Kozma M, Molnar K, et al. Breast adenocarcinoma-derived exosomes lower first-contact de-adhesion strength of adenocarcinoma cells to brain endothelial layer. Colloids Surf B Biointerfaces. 2021; 204: 111810.

[418] Csonti K, Fazakas C, Molnar K, Wilhelm I, Krizbai IA, Vegh AG. Breast adenocarcinoma cells adhere stronger to brain pericytes than to endothelial cells. Colloids Surf B Biointerfaces. 2024; 234: 113751.

[419] Santos L, Tomatis F, Ferreira HRS, et al. ENPP1 induces blood-brain barrier dysfunction and promotes brain metastasis formation in HER2-positive breast cancer. Neuro Oncol. 2024.

[420] Kirchner J, Volker E, Shityakov S, Saji S, Forster CY. Protecting the brain: novel strategies for preventing breast cancer brain metastases through selective estrogen receptor beta agonists and in vitro blood-brain barrier models. Int J Mol Sci. 2024; 25(6): 3379.

[421] Galloni C, Egnuni T, Zahed Mohajerani S, et al. Brain endothelial cells promote breast cancer cell extravasation to the brain via EGFR-DOCK4-RAC1 signalling. Commun Biol. 2024; 7(1): 602.

[422] Pan JK, Lin CH, Kuo YL, et al. MiR-211 determines brain metastasis specificity through SOX11/NGN2 axis in triple-negative breast cancer. Oncogene. 2021; 40(9): 1737-1751.

[423] Ippolitov D, Arreza L, Munir MN, Hombach-Klonisch S. Brain microvascular pericytes-more than bystanders in breast cancer brain metastasis. Cells. 2022; 11(8): 1263.

[424] Whiteley AE, Ma D, Wang L, et al. Breast cancer exploits neural signaling pathways for bone-to-meninges metastasis. Science. 2024; 384(6702): eadh5548.

[425] Song Q, Ruiz J, Xing F, et al. Single-cell sequencing reveals the landscape of the human brain metastatic microenvironment. Commun Biol. 2023; 6(1): 760.

[426] Deshpande K, Martirosian V, Nakamura BN, et al. Neuronal exposure induces neurotransmitter signaling and synaptic mediators in tumors early in brain metastasis. Neuro Oncol. 2022; 24(6): 914-924.

[427] Deshpande K, Martirosian V, Nakamura BN, et al. SRRM4-mediated REST to REST4 dysregulation promotes tumor growth and neural adaptation in breast cancer leading to brain metastasis. Neuro Oncol. 2024; 26(2): 309-322.

[428] Meszaros A, Molnar K, Fazakas C, et al. Inflammasome activation in peritumoral astrocytes is a key player in breast cancer brain metastasis development. Acta Neuropathol Commun. 2023; 11(1): 155.

[429] Dai J, Cimino PJ, Gouin KH, 3rd, et al. Astrocytic laminin-211 drives disseminated breast tumor cell dormancy in brain. Nat Cancer. 2022; 3(1): 25-42.

[430] Sirkisoon SR, Wong GL, Aguayo NR, et al. Breast cancer extracellular vesicles-derived miR-1290 activates astrocytes in the brain metastatic microenvironment via the FOXA2→CNTF axis to promote progression of brain metastases. Cancer Lett. 2022; 540: 215726.

[431] Foo SL, Sachaphibulkij K, Lee CLY, et al. Breast cancer metastasis to brain results in recruitment and activation of microglia through annexin-A1/formyl peptide receptor signaling. Breast Cancer Res. 2022; 24(1): 25.

[432] Rivera-Ramos A, Cruz-Hernandez L, Talaveron R, et al. Galectin-3 depletion tames pro-tumoural microglia and restrains cancer cells growth. Cancer Lett. 2024; 591: 216879.

[433] Wu SY, Sharma S, Wu K, et al. Tamoxifen suppresses brain metastasis of estrogen receptor-deficient breast cancer by skewing microglia polarization and enhancing their immune functions. Breast Cancer Res. 2021; 23(1): 35.

[434] Huang G, Wu Y, Gan H, Chu L. Overexpression of CD2/CD27 could inhibit the activation of nitrogen metabolism pathways and suppress M2 polarization of macrophages, thereby preventing brain metastasis of breast cancer. Transl Oncol. 2023; 37: 101768.

[435] Tong F, Hu H, Xu Y, et al. Hollow copper sulfide nanoparticles carrying ISRIB for the sensitized photothermal therapy of breast cancer and brain metastases through inhibiting stress granule formation and reprogramming tumor-associated macrophages. Acta Pharm Sin B. 2023; 13(8): 3471-3488.

[436] Adhikari E, Liu Q, Johnson J, et al. Brain metastasis-associated fibroblasts secrete fucosylated PVR/CD155 that induces breast cancer invasion. Cell Rep. 2023; 42(12): 113463.

[437] Xiao L, Zhou J, Liu H, et al. RNA sequence profiling reveals unique immune and metabolic features of breast cancer brain metastases. Front Oncol. 2021; 11: 679262.

[438] Yoshimura T, Li C, Wang Y, Matsukawa A. The chemokine monocyte chemoattractant protein-1/CCL2 is a promoter of breast cancer metastasis. Cell Mol Immunol. 2023; 20(7): 714-738.

[439] Nazari H, Cho AN, Goss D, Thiery JP, Ebrahimi Warkiani M. Impact of brain organoid-derived sEVs on metastatic adaptation and invasion of breast carcinoma cells through a microphysiological system. Lab Chip. 2024; 24(14): 3434-3455.

[440] Liu Y, Smith MR, Wang Y, et al. c-Met mediated cytokine network promotes brain metastasis of breast cancer by remodeling neutrophil activities. Cancers (Basel). 2023; 15(9): 2626.

[441] Geissler M, Jia W, Kiraz EN, et al. The brain pre-metastatic niche: biological and technical advancements. Int J Mol Sci. 2023; 24(12): 10055.

[442] Ye L, Wu Y, Zhou J, Xie M, Zhang Z, Su C. Influence of exosomes on astrocytes in the pre-metastatic niche of lung cancer brain metastases. Biol Proced Online. 2023; 25(1): 5.

[443] Guldner IH, Wang Q, Yang L, et al. CNS-native myeloid cells drive immune suppression in the brain metastatic niche through Cxcl10. Cell. 2020; 183(5): 1234-1248. e25.

[444] Ahuja S, Lazar IM. Proteomic insights into breast cancer response to brain cell-secreted factors. Sci Rep. 2024; 14(1): 19351.

[445] Carvalho R, Santos L, Conde I, et al. Nerve growth factor inducible (VGF) is a secreted mediator for metastatic breast cancer tropism to the brain. J Pathol. 2024; 264(2): 132-147.

[446] Turker E, Andrade Mier MS, Faber J, et al. Breast tumor cell survival and morphology in a brain-like extracellular matrix depends on matrix composition and mechanical properties. Adv Biol (Weinh). 2024:e2400184.

[447] Chang G, Shi L, Ye Y, et al. YTHDF3 induces the translation of m(6)A-enriched gene transcripts to promote breast cancer brain metastasis. Cancer Cell. 2020; 38(6): 857-871. e7.

[448] Souza VGP, Forder A, Telkar N, et al. Identifying new contributors to brain metastasis in lung adenocarcinoma: a transcriptomic meta-analysis. Cancers (Basel). 2023; 15(18): 4526.

[449] Wischnewski V, Maas RR, Aruffo PG, et al. Phenotypic diversity of T cells in human primary and metastatic brain tumors revealed by multiomic interrogation. Nat Cancer. 2023; 4(6): 908-924.

[450] Fares J, Cordero A, Kanojia D, Lesniak MS. The network of cytokines in brain metastases. Cancers (Basel). 2021; 13(1): 142.

[451] Maurya SK, Khan P, Rehman AU, et al. Rethinking the chemokine cascade in brain metastasis: preventive and therapeutic implications. Semin Cancer Biol. 2022; 86(Pt 3): 914-930.

[452] Woldmar N, Schwendenwein A, Kuras M, et al. Proteomic analysis of brain metastatic lung adenocarcinoma reveals intertumoral heterogeneity and specific alterations associated with the timing of brain metastases. ESMO Open. 2023; 8(1): 100741.

[453] Wang Y, Geller AE, Yan J. Spatial TIME landscape and its prognostic value in the lung and brain tumor: location matters. Signal Transduct Target Ther. 2023; 8(1): 192.

[454] Giannoudis A, Vareslija D, Sharma V, et al. Characterisation of the immune microenvironment of primary breast cancer and brain metastasis reveals depleted T-cell response associated to ARG2 expression. ESMO Open. 2022; 7(6): 100636.

[455] Sajjadi SF, Salehi N, Sadeghi M. Comprehensive integrated single-cell RNA sequencing analysis of brain metastasis and glioma microenvironment: Contrasting heterogeneity landscapes. PLoS One. 2024; 19(7): e0306220.

[456] Griguolo G, Tosi A, Dieci MV, et al. A comprehensive profiling of the immune microenvironment of breast cancer brain metastases. Neuro Oncol. 2022; 24(12): 2146-2158.

[457] Baschnagel AM, Elnaggar JH, VanBeek HJ, et al. ATR inhibitor M6620 (VX-970) enhances the effect of radiation in non-small cell lung cancer brain metastasis patient-derived xenografts. Mol Cancer Ther. 2021; 20(11): 2129-2139.

[458] Ji M, Wang D, Lin S, et al. A novel PI3K inhibitor XH30 suppresses orthotopic glioblastoma and brain metastasis in mice models. Acta Pharm Sin B. 2022; 12(2): 774-786.

[459] Eichner LJ, Curtis SD, Brun SN, et al. HDAC3 is critical in tumor development and therapeutic resistance in Kras-mutant non-small cell lung cancer. Sci Adv. 2023; 9(11): eadd3243.

[460] Gentzler RD, Villaruz LC, Rhee JC, et al. Phase I study of entinostat, atezolizumab, carboplatin, and etoposide in previously untreated extensive-stage small cell lung cancer, ETCTN 10399. Oncologist. 2023; 28(11): 1007-e1107.

[461] Johnson ML, Strauss J, Patel MR, et al. Mocetinostat in combination with durvalumab for patients with advanced NSCLC: results from a phase I/II study. Clin Lung Cancer. 2023; 24(3): 218-227.

[462] Mao J, Ni J, Chu L, et al. Pamiparib as consolidation treatment after concurrent chemoradiotherapy of limited-stage small cell lung cancer: a single-arm, open-label phase 2 trial. Radiat Oncol. 2024; 19(1): 47.

[463] Chabot P, Hsia TC, Ryu JS, et al. Veliparib in combination with whole-brain radiation therapy for patients with brain metastases from non-small cell lung cancer: results of a randomized, global, placebo-controlled study. J Neurooncol. 2017; 131(1): 105-115.

[464] Park S, Baldry R, Jung HA, et al. Phase II efficacy and safety of 80 mg osimertinib in patients with leptomeningeal metastases associated with epidermal growth factor receptor mutation-positive non-small cell lung cancer (BLOSSOM). J Clin Oncol. 2024; 42(23): 2747-2756.

[465] Lu S, Zhang Y, Zhang G, et al. Befotertinib for patients with pretreated EGFR T790M mutated locally advanced or metastatic NSCLC: Final overall survival results from a phase 2 trial. Lung Cancer. 2024; 195: 107901.

[466] Morise M, Kato T, Matsumoto S, et al. Long-term experience with tepotinib in Japanese patients with MET exon 14 skipping NSCLC from the Phase II VISION study. Cancer Sci. 2024; 115(4): 1296-1305.

[467] Cheng Y, Huang D, Zhou J, et al. Intracranial activity of selpercatinib in chinese patients with advanced RET fusion-positive non-small-cell lung cancer in the phase II LIBRETTO-321 trial. JCO Precis Oncol. 2023; 7: e2200708.

[468] Lu S, Pan H, Wu L, et al. Efficacy, safety and pharmacokinetics of Unecritinib (TQ-B3101) for patients with ROS1 positive advanced non-small cell lung cancer: a Phase I/II Trial. Signal Transduct Target Ther. 2023; 8(1): 249.

[469] Jung HA, Park S, Lee SH, Ahn JS, Ahn MJ, Sun JM. Dacomitinib in EGFR-mutant non-small-cell lung cancer with brain metastasis: a single-arm, phase II study. ESMO Open. 2023; 8(6): 102068.

[470] Shi Y, Wu S, Wang K, et al. Efficacy and safety of rezivertinib (BPI-7711) in patients with locally advanced or metastatic/recurrent EGFR T790M-mutated NSCLC: a phase 2b study. J Thorac Oncol. 2022; 17(11): 1306-1317.

[471] Tan DSW, Kim SW, Ponce Aix S, et al. Nazartinib for treatment-naive EGFR-mutant non-small cell lung cancer: results of a phase 2, single-arm, open-label study. Eur J Cancer. 2022; 172: 276-286.

[472] Zwierenga F, van Veggel B, Hendriks LEL, et al. High dose osimertinib in patients with advanced stage EGFR exon 20 mutation-positive NSCLC: Results from the phase 2 multicenter POSITION20 trial. Lung Cancer. 2022; 170: 133-140.

[473] Zhou Q, Wang M, Zhang H, et al. Safety and efficacy of epitinib for EGFR-mutant non-small cell lung cancer with brain metastases: open-label multicentre dose-expansion phase Ib study. Clin Lung Cancer. 2022; 23(6): e353-e361.

[474] Dagogo-Jack I, Oxnard GR, Evangelist M, et al. Phase II study of lorlatinib in patients with anaplastic lymphoma kinase-positive lung cancer and CNS-specific relapse. JCO Precis Oncol. 2022; 6: e2100522.

[475] Lu S, Zhou Q, Liu X, et al. Lorlatinib for previously treated ALK-positive advanced NSCLC: primary efficacy and safety from a phase 2 study in People’s Republic of China. J Thorac Oncol. 2022; 17(6): 816-826.

[476] Song Z, Li Y, Chen S, et al. Efficacy and safety of pyrotinib in advanced lung adenocarcinoma with HER2 mutations: a multicenter, single-arm, phase II trial. BMC Med. 2022; 20(1): 42.

[477] Cho BC, Han JY, Kim SW, et al. A phase 1/2 study of lazertinib 240 mg in patients with advanced EGFR T790M-positive NSCLC after previous EGFR tyrosine kinase inhibitors. J Thorac Oncol. 2022; 17(4): 558-567.

[478] Le X, Sakai H, Felip E, et al. Tepotinib efficacy and safety in patients with MET exon 14 skipping NSCLC: outcomes in patient subgroups from the VISION study with relevance for clinical practice. Clin Cancer Res. 2022; 28(6): 1117-1126.

[479] Song Z, Lv D, Chen SQ, et al. Pyrotinib in patients with HER2-amplified advanced non-small cell lung cancer: a prospective, multicenter, single-arm trial. Clin Cancer Res. 2022; 28(3): 461-467.

[480] Ma Y, Zhao H, Xue J, et al. First-in-human phase I study of TQ-B3139 (CT-711) in advanced non-small cell lung cancer patients with ALK and ROS1 rearrangements. Eur J Cancer. 2022; 173: 238-249.

[481] Wang P, Li Y, Lv D, et al. Mefatinib as first-line treatment of patients with advanced EGFR-mutant non-small-cell lung cancer: a phase Ib/II efficacy and biomarker study. Signal Transduct Target Ther. 2021; 6(1): 374.

[482] Stinchcombe TE, Doebele RC, Wang X, Gerber DE, Horn L, Camidge DR. Preliminary clinical and molecular analysis results from a single-arm phase 2 trial of brigatinib in patients with disease progression after next-generation ALK tyrosine kinase inhibitors in advanced ALK+ NSCLC. J Thorac Oncol. 2021; 16(1): 156-161.

[483] Yamaguchi H, Wakuda K, Fukuda M, et al. A phase II study of osimertinib for radiotherapy-naive central nervous system metastasis from NSCLC: results for the T790M cohort of the OCEAN study (LOGIK1603/WJOG9116L). J Thorac Oncol. 2021; 16(12): 2121-2132.

[484] Subbiah V, Gainor JF, Oxnard GR, et al. Intracranial efficacy of selpercatinib in RET fusion-positive non-small cell lung cancers on the LIBRETTO-001 trial. Clin Cancer Res. 2021; 27(15): 4160-4167.

[485] Eide IJZ, Grut H, Helland A, et al. Intracranial effect of osimertinib in relapsed EGFR-mutated T790M-positive and -negative non-small cell lung cancer patients: results from a phase II study. Acta Oncol. 2021; 60(12): 1565-1571.

[486] Fan C, Jiang Z, Teng C, et al. Efficacy and safety of intrathecal pemetrexed for TKI-failed leptomeningeal metastases from EGFR+ NSCLC: an expanded, single-arm, phase II clinical trial. ESMO Open. 2024; 9(4): 102384.

[487] Lee Y, Kim HR, Hong MH, et al. A randomized Phase 2 study to compare erlotinib with or without bevacizumab in previously untreated patients with advanced non-small cell lung cancer with EGFR mutation. Cancer. 2023; 129(3): 405-414.

[488] Yang G, Xu H, Yang Y, et al. Pyrotinib combined with apatinib for targeting metastatic non-small cell lung cancer with HER2 alterations: a prospective, open-label, single-arm phase 2 study (PATHER2). BMC Med. 2022; 20(1): 277.

[489] Watanabe S, Furuya N, Nakamura A, et al. A phase II study of atezolizumab with bevacizumab, carboplatin, and paclitaxel for patients with EGFR-mutated NSCLC after TKI treatment failure (NEJ043 study). Eur J Cancer. 2024; 197: 113469.

[490] Tanimura K, Uchino J, Kimura H, et al. Ramucirumab plus docetaxel for patients with non-small cell lung cancer with brain metastases: a multicenter, open-label single-arm phase II trial. Oncologist. 2023; 28(6): 551-e454.

[491] Kaneda H, Sawa K, Daga H, et al. Phase 1b study of ramucirumab in combination with erlotinib or osimertinib for untreated EGFR-mutated non-small cell lung cancer patients with asymptomatic brain metastases. Invest New Drugs. 2021; 39(6): 1598-1603.

[492] Li Z, Wang J, Deng L, et al. Hippocampal avoidance whole-brain radiotherapy with simultaneous integrated boost in lung cancer brain metastases and utility of the Hopkins verbal learning test for testing cognitive impairment in Chinese patients: a prospective phase II study. BMC Cancer. 2024; 24(1): 899.

[493] Yang JT, Wijetunga NA, Pentsova E, et al. Randomized phase II trial of proton craniospinal irradiation versus photon involved-field radiotherapy for patients with solid tumor leptomeningeal metastasis. J Clin Oncol. 2022; 40(33): 3858-3867.

[494] Suzuki K, Shiono S, Hasumi T, et al. Clinical significance of bifocal treatment for synchronous brain metastasis in T1-2 non-small-cell lung cancers: JNETS0301. Gen Thorac Cardiovasc Surg. 2021; 69(6): 967-975.

[495] Altan M, Wang Y, Song J, et al. Nivolumab and ipilimumab with concurrent stereotactic radiosurgery for intracranial metastases from non-small cell lung cancer: analysis of the safety cohort for non-randomized, open-label, phase I/II trial. J Immunother Cancer. 2023; 11(7): e006871.

[496] Verry C, Dufort S, Villa J, et al. Theranostic AGuIX nanoparticles as radiosensitizer: A phase I, dose-escalation study in patients with multiple brain metastases (NANO-RAD trial). Radiother Oncol. 2021; 160: 159-165.

[497] Kumthekar PU, Avram MJ, Lassman AB, et al. A phase I/II study of intrathecal trastuzumab in human epidermal growth factor receptor 2-positive (HER2-positive) cancer with leptomeningeal metastases: Safety, efficacy, and cerebrospinal fluid pharmacokinetics. Neuro Oncol. 2023; 25(3): 557-565.

[498] Oberkampf F, Gutierrez M, Trabelsi Grati O, et al. Phase II study of intrathecal administration of trastuzumab in patients with HER2-positive breast cancer with leptomeningeal metastasis. Neuro Oncol. 2023; 25(2): 365-374.

[499] Perez-Garcia JM, Vaz Batista M, Cortez P, et al. Trastuzumab deruxtecan in patients with central nervous system involvement from HER2-positive breast cancer: The DEBBRAH trial. Neuro Oncol. 2023; 25(1): 157-166.

[500] Bartsch R, Berghoff AS, Furtner J, et al. Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial. Nat Med. 2022; 28(9): 1840-1847.

[501] Sachdev JC, Munster P, Northfelt DW, et al. Phase I study of liposomal irinotecan in patients with metastatic breast cancer: findings from the expansion phase. Breast Cancer Res Treat. 2021; 185(3): 759-771.

[502] Xie Y, Gong C, Zhang J, et al. Phase II trail of nab-paclitaxel in metastatic breast cancer patients with visceral metastases. BMC Cancer. 2021; 21(1): 1174.

[503] Brastianos PK, Kim AE, Giobbie-Hurder A, et al. Pembrolizumab in brain metastases of diverse histologies: phase 2 trial results. Nat Med. 2023; 29(7): 1728-1737.

[504] Lin NU, Pegram M, Sahebjam S, et al. Pertuzumab plus high-dose trastuzumab in patients with progressive brain metastases and HER2-positive metastatic breast cancer: primary analysis of a phase II study. J Clin Oncol. 2021; 39(24): 2667-2675.

[505] Lin NU, Murthy RK, Abramson V, et al. Tucatinib vs placebo, both in combination with trastuzumab and capecitabine, for previously treated ERBB2 (HER2)-positive metastatic breast cancer in patients with brain metastases: updated exploratory analysis of the HER2CLIMB randomized clinical trial. JAMA Oncol. 2023; 9(2): 197-205.

[506] Xie XF, Zhang QY, Huang JY, et al. Pyrotinib combined with trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2-positive metastatic breast cancer: a single-arm exploratory phase II trial. Breast Cancer Res Treat. 2023; 197(1): 93-101.

[507] Shah AN, Santa-Maria CA, Mukhija D, et al. A phase II single-arm study of palbociclib in patients with HER2-positive breast cancer with brain metastases and analysis of ctDNA in patients with active brain metastases. Clin Breast Cancer. 2023; 23(3): 324-329.

[508] Phillips C, Pinkham MB, Moore A, et al. Local hero: A phase II study of local therapy only (stereotactic radiosurgery and /or surgery) for treatment of up to five brain metastases from HER2+ breast cancer. (TROG study 16.02). Breast. 2024; 74: 103675.

[509] Yang TJ, Wijetunga NA, Yamada J, et al. Clinical trial of proton craniospinal irradiation for leptomeningeal metastases. Neuro Oncol. 2021; 23(1): 134-143.

[510] Chen TW, Dai MS, Tseng LM, et al. Whole-brain radiotherapy alone vs preceded by bevacizumab, etoposide, and cisplatin for untreated brain metastases from breast cancer: a randomized clinical trial. JAMA Oncol. 2024; 10(3): 325-334.

[511] Kim IA, Winter KA, Sperduto PW, et al. Concurrent lapatinib with brain radiation therapy in patients with HER2+ breast cancer with brain metastases: NRG oncology-KROG/RTOG 1119 phase 2 randomized trial. Int J Radiat Oncol Biol Phys. 2024; 118(5): 1391-1401.

[512] Yang Z, Meng J, Mei X, et al. Brain radiotherapy with pyrotinib and capecitabine in patients with ERBB2-positive advanced breast cancer and brain metastases: a nonrandomized phase 2 trial. JAMA Oncol. 2024; 10(3): 335-341.

[513] Morikawa A, Grkovski M, Patil S, et al. A phase I trial of sorafenib with whole brain radiotherapy (WBRT) in breast cancer patients with brain metastases and a correlative study of FLT-PET brain imaging. Breast Cancer Res Treat. 2021; 188(2): 415-425.

[514] Izraely S, Ben-Menachem S, Malka S, et al. The vicious cycle of melanoma-microglia crosstalk: inter-melanoma variations in the brain-metastasis-promoting IL-6/JAK/STAT3 signaling pathway. Cells. 2023; 12(11): 1513.

[515] Addeo R. Silibinin: a new opportunity for the treatment of brain metastasis from lung cancer. J Exp Pharmacol. 2021; 13: 901-903.

[516] Verdura S, Cuyas E, Ruiz-Torres V, et al. Lung cancer management with silibinin: a historical and translational perspective. Pharmaceuticals (Basel). 2021; 14(6): 559.

[517] Tanzhu G, Chen L, Xiao G, et al. The schemes, mechanisms and molecular pathway changes of tumor treating fields (TTFields) alone or in combination with radiotherapy and chemotherapy. Cell Death Discov. 2022; 8(1): 416.

[518] Salvador E, Kessler AF, Hörmann J, et al. Abstract 6251: blood brain barrier opening by TTFields: a future CNS drug delivery strategy. Cancer Research. 2020; 80(16_Supplement): 6251-6251.

[519] Brami CT, Salvador E, Kessler AF, et al. Transient opening of the blood brain barrier by tumor treating fields (TTFields). Cancer Research. 2021; 81(13).

[520] Salvador E, Kessler A, Hoermann J, et al. Tumor treating fields effects on the blood-brain barrier in vitro and in vivo. Journal of Clinical Oncology. 2020; 38(15_suppl): 2551-2551.

[521] Schulz E, Kessler AF, Salvador E, et al. EXTH-02. the blood brain barrier (BBB) permeability is altered by tumor treating fields (TTFIELDS) in vivo. Neuro-Oncology. 2019; 21(Supplement_6): vi82-vi82.

[522] Kessler AF, Schaeffer CM, Burek M, et al. Abstract 252: tumor treating fields (TTFields) affect blood brain barrier (BBB) integrity in vitro and in vivo. Cancer Res. 2019; 79(13_Supplement): 252-252.

[523] Kessler AF, Schaeffer C, Burek M, et al. P04.33 EFFECTS of tumor treating fields (TTFields) on blood brain barrier (BBB) permeability. Neuro-Oncology. 2018; 20(suppl_3): iii286-iii286.

[524] Stupp R, Kanner A, Engelhard H, et al. A prospective, randomized, open-label, phase III clinical trial of NovoTTF-100A versus best standard of care chemotherapy in patients with recurrent glioblastoma. J Clin Oncol. 2010; 28(18_suppl): LBA2007-LBA2007.

[525] Zhu J-J, O’Donnell RT, Goldlust S, Ram Z. CTNI-77. EF-19, a post-approval registry study of tumor treating fields (TTFIELDS) in recurrent glioblastoma (rGBM). Neuro-Oncology. 2020; 22(Supplement_2): ii60-ii60.

[526] Stupp R, Wong ET, Kanner AA, et al. NovoTTF-100A versus physician’s choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer. 2012; 48(14): 2192-202.

[527] Brozova H, Lucas A, Salmaggi A, Vymazal J. BMET-06COMET: a phase II randomized study of ttfields versus supportive care in non-small cell lung cancer patients with 1–5 brain metastases - initial safety results. Neuro-Oncology. 2015; 17(suppl_5): v46-v46.

[528] Bernard-Arnoux F, Lamure M, Ducray F, Aulagner G, Honnorat J, Armoiry X. The cost-effectiveness of tumor-treating fields therapy in patients with newly diagnosed glioblastoma. Neuro Oncol. 2016; 18(8): 1129-36.

[529] Connock M, Auguste P, Dussart C, Guyotat J, Armoiry X. Cost-effectiveness of tumor-treating fields added to maintenance temozolomide in patients with glioblastoma: an updated evaluation using a partitioned survival model. J Neurooncol. 2019; 143(3): 605-611.

[530] Guzauskas GF, Pollom EL, Stieber VW, Wang BCM, Garrison LP, Jr. Tumor treating fields and maintenance temozolomide for newly-diagnosed glioblastoma: a cost-effectiveness study. J Med Econ. 2019; 22(10): 1006-1013.

[531] Tian W, Ning J, Chen L, et al. Cost-effectiveness of tumor-treating fields plus standard therapy for advanced non-small cell lung cancer progressed after platinum-based therapy in the United States. Front Pharmacol. 2024; 15: 1333128.

[532] Marks S, Naidoo J. Antibody drug conjugates in non-small cell lung cancer: an emerging therapeutic approach. Lung Cancer. 2022; 163: 59-68.

[533] Desai A, Abdayem P, Adjei AA, Planchard D. Antibody-drug conjugates: a promising novel therapeutic approach in lung cancer. Lung Cancer. 2022; 163: 96-106.

[534] Tomasich E, Steindl A, Paiato C, et al. Frequent overexpression of HER3 in brain metastases from breast and lung cancer. Clin Cancer Res. 2023; 29(16): 3225-3236.

[535] Kabraji S, Lin NU. Keeping it in the family: HER3 as a target in brain metastases. Clin Cancer Res. 2023; 29(16): 2961-2963.

[536] Kumthekar P, Tang SC, Brenner AJ, et al. ANG1005, a brain-penetrating peptide-drug conjugate, shows activity in patients with breast cancer with leptomeningeal carcinomatosis and recurrent brain metastases. Clin Cancer Res. 2020; 26(12): 2789-2799.

[537] Hu X, Deng X, Xie J, et al. Evolutionary trend analysis of research on immunotherapy for brain metastasis based on machine-learning scientometrics. Pharmaceuticals (Basel). 2024; 17(7): 850.

[538] Chu X, Tian W, Wang Z, Zhang J, Zhou R. Co-inhibition of TIGIT and PD-1/PD-L1 in cancer immunotherapy: mechanisms and clinical trials. Mol Cancer. 2023; 22(1): 93.

[539] Chehade R, Qazi MA, Ennis M, et al. PD-L1 expression in breast cancer brain metastases. Neurooncol Adv. 2022; 4(1): vdac154.

[540] Schlam I, Gatti-Mays ME. Immune checkpoint inhibitors in the treatment of breast cancer brain metastases. Oncologist. 2022; 27(7): 538-547.

[541] Uceda-Castro R, Margarido AS, Cornet L, et al. Re-purposing the pro-senescence properties of doxorubicin to introduce immunotherapy in breast cancer brain metastasis. Cell Rep Med. 2022; 3(11): 100821.

[542] Carney CP, Pandey N, Kapur A, Woodworth GF, Winkles JA, Kim AJ. Harnessing nanomedicine for enhanced immunotherapy for breast cancer brain metastases. Drug Deliv Transl Res. 2021; 11(6): 2344-2370.

[543] Zhao Z, Li C, Zhang Y, et al. Nanomaterials with dual immunomodulatory functions for synergistic therapy of breast cancer brain metastases. Bioact Mater. 2023; 27: 474-487.

[544] Subham S, Jeppson JD, Worcester C, et al. EGFR as a potent CAR T target in triple negative breast cancer brain metastases. Breast Cancer Res Treat. 2023; 197(1): 57-69.

[545] Tao B, Du R, Zhang X, et al. Engineering CAR-NK cell derived exosome disguised nano-bombs for enhanced HER2 positive breast cancer brain metastasis therapy. J Control Release. 2023; 363: 692-706.

[546] Zhang J, McAndrew NP, Wang X, et al. Preclinical and clinical activity of DZD1516, a full blood-brain barrier-penetrant, highly selective HER2 inhibitor. Breast Cancer Res. 2023; 25(1): 81.

[547] Faure C, Djerbi-Bouillie R, Domingot A, et al. Allosteric inhibition of HER2 by moesin-mimicking compounds targets HER2-positive cancers and brain metastases. Cancer Res. 2021; 81(21): 5464-5476.

[548] Wang W, He H, Marin-Ramos NI, et al. Enhanced brain delivery and therapeutic activity of trastuzumab after blood-brain barrier opening by NEO100 in mouse models of brain-metastatic breast cancer. Neuro Oncol. 2021; 23(10): 1656-1667.

[549] Angeli E, Paris J, Le Tilly O, et al. A Fab of trastuzumab to treat HER2 overexpressing breast cancer brain metastases. Exp Hematol Oncol. 2024; 13(1): 41.

[550] Werner MS, Aras S, Morgan AR, et al. Adeno-associated virus-mediated trastuzumab delivery to the central nervous system for human epidermal growth factor receptor 2+ brain metastasis. Cancer Gene Ther. 2024; 31(5): 766-777.

[551] Silvestri VL, Tran AD, Chung M, et al. Distinct uptake and elimination profiles for trastuzumab, human IgG, and biocytin-TMR in experimental HER2+ brain metastases of breast cancer. Neuro Oncol. 2024; 26(6): 1067-1082.

[552] Arsiwala TA, Blethen KE, Wolford CP, et al. Blood-tumor barrier opening by MRI-guided transcranial focused ultrasound in a preclinical breast cancer brain metastasis model improves efficacy of combinatorial chemotherapy. Front Oncol. 2023; 13: 1104594.

[553] Johanssen VA, Ruan JL, Vince O, et al. Targeted opening of the blood-brain barrier using VCAM-1 functionalised microbubbles and “whole brain” ultrasound. Theranostics. 2024; 14(10): 4076-4089.

[554] Wei Y, Sun Y, Wei J, et al. Selective transferrin coating as a facile strategy to fabricate BBB-permeable and targeted vesicles for potent RNAi therapy of brain metastatic breast cancer in vivo. J Control Release. 2021; 337: 521-529.

[555] Gupta N, Srivastava SK. Atovaquone suppresses the growth of metastatic triple-negative breast tumors in lungs and brain by inhibiting integrin/FAK signaling axis. Pharmaceuticals (Basel). 2021; 14(6): 521.

[556] De Luca F, Roda E, Ratto D, et al. Fighting secondary triple-negative breast cancer in cerebellum: a powerful aid from a medicinal mushrooms blend. Biomed Pharmacother. 2023; 159: 114262.

[557] Ju X, Chen H, Miao T, Ni J, Han L. Prodrug delivery using dual-targeting nanoparticles to treat breast cancer brain metastases. Mol Pharm. 2021; 18(7): 2694-2702.

[558] Ngamcherdtrakul W, Bejan DS, Cruz-Munoz W, et al. Targeted nanoparticle for co-delivery of HER2 siRNA and a taxane to mirror the standard treatment of HER2+ Breast cancer: efficacy in breast tumor and brain metastasis. Small. 2022; 18(11): e2107550.

[559] Mu R, Sun H, Zeng Y, et al. Nanomodulators targeting endothelial WNT and pericytes to reversibly open the blood-tumor barrier for boosted brain tumor therapy. J Control Release. 2024; 369: 458-474.

[560] Ashokan A, Sarkar S, Kamran MZ, et al. Simultaneous targeting of peripheral and brain tumors with a therapeutic nanoparticle to disrupt metabolic adaptability at both sites. Proc Natl Acad Sci USA. 2024; 121(20): e2318119121.

[561] Tong Y, An P, Tang P, et al. Suppressing Wnt signaling of the blood–tumor barrier to intensify drug delivery and inhibit lipogenesis of brain metastases. Acta Pharm Sin B. 2024; 14(6): 2716-2731.

[562] Cavaco M, Perez-Peinado C, Valle J, et al. The use of a selective, nontoxic dual-acting peptide for breast cancer patients with brain metastasis. Biomed Pharmacother. 2024; 174: 116573.

[563] Goyette MA, Stevens LE, DePinho CR, et al. Cancer-stromal cell interactions in breast cancer brain metastases induce glycocalyx-mediated resistance to HER2-targeting therapies. Proc Natl Acad Sci USA. 2024; 121(20): e2322688121.

[564] Du J, Shao Y, Hu Y, et al. Multifunctional Liposomes Enable Active Targeting and Twinfilin 1 Silencing to Reverse Paclitaxel Resistance in Brain Metastatic Breast Cancer. ACS Appl Mater Interfaces. 2021; 13(20): 23396-23409.

[565] Zhao Z, Zhang Y, Li C, et al. Microenvironment-tailored micelles restrain carcinoma-astrocyte crosstalk for brain metastasis. J Control Release. 2022; 349: 520-532.

[566] Lu H, Chen T, Wang Y, He Y, Pang Z, Wang Y. Dual targeting micelles loaded with paclitaxel and lapatinib for combinational therapy of brain metastases from breast cancer. Sci Rep. 2022; 12(1): 2610.

[567] Menendez JA, Lupu R. Fatty acid synthase: a druggable driver of breast cancer brain metastasis. Expert Opin Ther Targets. 2022; 26(5): 427-444.

[568] Serhan HA, Bao L, Cheng X, et al. Targeting fatty acid synthase in preclinical models of TNBC brain metastases synergizes with SN-38 and impairs invasion. NPJ Breast Cancer. 2024; 10(1): 43.

[569] Esquea EM, Ciraku L, Young RG, et al. Selective and brain-penetrant ACSS2 inhibitors target breast cancer brain metastatic cells. Front Pharmacol. 2024; 15: 1394685.

[570] Benchama O, Tyukhtenko S, Malamas MS, Williams MK, Makriyannis A, Avraham HK. Inhibition of triple negative breast cancer-associated inflammation, tumor growth and brain colonization by targeting monoacylglycerol lipase. Sci Rep. 2022; 12(1): 5328.

[571] Cheng YJ, Fan F, Zhang Z, Zhang HJ. Lipid metabolism in malignant tumor brain metastasis: reprogramming and therapeutic potential. Expert Opin Ther Targets. 2023; 27(9): 861-878.

[572] Tundidor I, Seijo-Vila M, Blasco-Benito S, et al. Identification of fatty acid amide hydrolase as a metastasis suppressor in breast cancer. Nat Commun. 2023; 14(1): 3130.

[573] Lim M, Fletcher NL, Saunus JM, et al. Targeted hyperbranched nanoparticles for delivery of doxorubicin in breast cancer brain metastasis. Mol Pharm. 2023; 20(12): 6169-6183.

[574] Kitamura Y, Kanaya N, Moleirinho S, et al. Anti-EGFR VHH-armed death receptor ligand-engineered allogeneic stem cells have therapeutic efficacy in diverse brain metastatic breast cancers. Sci Adv. 2021; 7(10): eabe8671.

[575] Fan KY, Chehade R, Qazi M, Moravan V, Nofech-Mozes S, Jerzak KJ. Androgen receptor is expressed in the majority of breast cancer brain metastases and is subtype-dependent. Cancers (Basel). 2023; 15(10): 2748.

[576] Tomasik B, Bienkowski M, Gorska Z, et al. Molecular aspects of brain metastases in breast cancer. Cancer Treat Rev. 2023; 114: 102521.

[577] Li J, Zhen J, Ai R, Lai M, Wang H, Cai L. Intracranial management of HER-2 overexpression breast cancer with extensive volume or symptomatic brain metastases. Front Oncol. 2024; 14: 1386909.

[578] Mashiach E, Alzate JD, De Nigris Vasconcellos F, et al. Long-term survival from breast cancer brain metastases in the era of modern systemic therapies. Neurosurgery. 2024; 94(1): 154-164.

[579] Laakmann E, Witzel I, Neunhoffer T, et al. Characteristics of patients with brain metastases from human epidermal growth factor receptor 2-positive breast cancer: subanalysis of Brain Metastases in Breast Cancer Registry. ESMO Open. 2022; 7(3): 100495.

[580] Nie Y, Ying B, Lu Z, Sun T, Sun G. Predicting survival and prognosis of postoperative breast cancer brain metastasis: a population-based retrospective analysis. Chin Med J (Engl). 2023; 136(14): 1699-1707.

[581] Pereslete AM, Hughes ME, Martin AR, et al. Analysis of HER2 expression changes from breast primary to brain metastases and the impact of HER2-low expression on overall survival. Neuro Oncol. 2024.

[582] Muller V, Bartsch R, Lin NU, Montemurro F, Pegram MD, Tolaney SM. Epidemiology, clinical outcomes, and unmet needs of patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases: a systematic literature review. Cancer Treat Rev. 2023; 115: 102527.

[583] Tini P, Marampon F, Giraffa M, et al. Current status and perspectives of interventional clinical trials for brain metastases: analysis of ClinicalTrials.gov. Radiat Oncol. 2023; 18(1): 62.

[584] Epaillard N, Bassil J, Pistilli B. Current indications and future perspectives for antibody-drug conjugates in brain metastases of breast cancer. Cancer Treat Rev. 2023; 119: 102597.

[585] Zeng Y, Hu CH, Li YZ, et al. Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer. Nat Med. 2024; 30(6): 1680-1688.

[586] Arjuna S, Shah M, Dono A, et al. Rapid detection of mutations in CSF-cfTNA with the genexus integrated sequencer. J Neurooncol. 2024; 166(1): 39-49.

[587] Lipkova J, Chen RJ, Chen B, et al. Artificial intelligence for multimodal data integration in oncology. Cancer Cell. 2022; 40(10): 1095-1110.

[588] Cacho-Diaz B, Valdes-Ferrer SI, Chavez-MacGregor M, Salmeron-Moreno K, Villarreal-Garza C, Reynoso-Noveron N. Brain metastasis risk prediction model in females with hormone receptor-positive breast cancer. Radiother Oncol. 2024; 197: 110379.

[589] Lee RY, Wu Y, Goh D, et al. Application of artificial intelligence to in vitro tumor modeling and characterization of the tumor microenvironment. Adv Healthc Mater. 2023; 12(14): e2202457.

[590] Cho S, Joo B, Park M, et al. A radiomics-based model for potentially more accurate identification of subtypes of breast cancer brain metastases. Yonsei Med J. 2023; 64(9): 573-580.

[591] Garcia-Recio S, Hinoue T, Wheeler GL, et al. Multiomics in primary and metastatic breast tumors from the AURORA US network finds microenvironment and epigenetic drivers of metastasis. Nat Cancer. 2023; 4(1): 128-147.

[592] Gong Z, Xu T, Peng N, et al. A multi-center, multi-parametric MRI dataset of primary and secondary brain tumors. Sci Data. 2024; 11(1): 789.

[593] Khan MS, Wong GL, Zhuang C, Najjar MK, Lo HW. Crosstalk between breast cancer-derived microRNAs and brain microenvironmental cells in breast cancer brain metastasis. Front Oncol. 2024; 14: 1436942.

[594] Figueira I, Godinho-Pereira J, Galego S, et al. MicroRNAs and extracellular vesicles as distinctive biomarkers of precocious and advanced stages of breast cancer brain metastases development. Int J Mol Sci. 2021; 22(10): 5214.

[595] Cicero J, Trouvilliez S, Palma M, et al. ProNGF promotes brain metastasis through TrkA/EphA2 induced Src activation in triple negative breast cancer cells. Exp Hematol Oncol. 2023; 12(1): 104.

[596] Ni J, Miao T, Su M, et al. PSMA-targeted nanoparticles for specific penetration of blood-brain tumor barrier and combined therapy of brain metastases. J Control Release. 2021; 329: 934-947.

[597] Ju X, Miao T, Chen H, Ni J, Han L. Overcoming Mfsd2a-mediated low transcytosis to boost nanoparticle delivery to brain for chemotherapy of brain metastases. Adv Healthc Mater. 2021; 10(9): e2001997.

[598] Grote I, Poppe A, Lehmann U, Christgen M, Kreipe H, Bartels S. Frequency of genetic alterations differs in advanced breast cancer between metastatic sites. Genes Chromosomes Cancer. 2024; 63(1): e23199.

[599] Nolan E, Kang Y, Malanchi I. Mechanisms of organ-specific metastasis of breast cancer. Cold Spring Harb Perspect Med. 2023; 13(11): a041326.

[600] Kim MM, Mehta MP, Smart DK, et al. National Cancer Institute Collaborative Workshop on shaping the landscape of brain metastases research: challenges and recommended priorities. Lancet Oncol. 2023; 24(8): e344-e354.

[601] Fleege NMG, Pierce-Gjeldum D, Swartz LK, et al. IMPACT the brain: a team-based approach to management of metastatic breast cancer with CNS metastases. JCO Oncol Pract. 2023; 19(1): e67-e77.

[602] Moss NS, Beal K, Tabar V. Brain metastasis—a distinct oncologic disease best served by an integrated multidisciplinary team approach. JAMA Oncol. 2022; 8(9): 1252-1254.

RIGHTS & PERMISSIONS

2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.