Patient-derived xenograft model in cancer: establishment and applications

Ao Gu , Jiatong Li , Meng-Yao Li , Yingbin Liu

MedComm ›› 2025, Vol. 6 ›› Issue (2) : e70059

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MedComm ›› 2025, Vol. 6 ›› Issue (2) : e70059 DOI: 10.1002/mco2.70059
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Patient-derived xenograft model in cancer: establishment and applications

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Abstract

The patient-derived xenograft (PDX) model is a crucial in vivo model extensively employed in cancer research that has been shown to maintain the genomic characteristics and pathological structure of patients across various subtypes, metastatic, and diverse treatment histories. Various treatment strategies utilized in PDX models can offer valuable insights into the mechanisms of tumor progression, drug resistance, and the development of novel therapies. This review provides a comprehensive overview of the establishment and applications of PDX models. We present an overview of the history and current status of PDX models, elucidate the diverse construction methodologies employed for different tumors, and conduct a comparative analysis to highlight the distinct advantages and limitations of this model in relation to other in vivo models. The applications are elucidated in the domain of comprehending the mechanisms underlying tumor development and cancer therapy, which highlights broad applications in the fields of chemotherapy, targeted therapy, delivery systems, combination therapy, antibody–drug conjugates and radiotherapy. Furthermore, the combination of the PDX model with multiomics and single-cell analyses for cancer research has also been emphasized. The application of the PDX model in clinical treatment and personalized medicine is additionally emphasized.

Keywords

cancer / multiomics / patient-derived xenograft model / therapy / tumor progress

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Ao Gu, Jiatong Li, Meng-Yao Li, Yingbin Liu. Patient-derived xenograft model in cancer: establishment and applications. MedComm, 2025, 6(2): e70059 DOI:10.1002/mco2.70059

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References

[1]

Ramos Zapatero M, Tong A, Opzoomer JW, et al. Trellis tree-based analysis reveals stromal regulation of patient-derived organoid drug responses. Cell. 2023; 186(25): 5606-5619.

[2]

Le Magnen C, Dutta A, Abate-Shen C. Optimizing mouse models for precision cancer prevention. Nat Rev Cancer. 2016; 16(3): 187-196.

[3]

AlMusawi S, Ahmed M, Nateri AS. Understanding cell-cell communication and signaling in the colorectal cancer microenvironment. Clin Transl Med. 2021; 11(2): e308.

[4]

Gu A, Li J, Qiu S, et al. Pancreatic cancer environment: from patient-derived models to single-cell omics. Mol Omics. 2024; 20(4): 220-233.

[5]

Tao JX, Zhu L, Yakoub M, Reissfelder C, Loges S, Schölch S, Cell-cell interactions drive metastasis of circulating tumor microemboli. Cancer Res. 2022; 82(15): 2661-2671.

[6]

Lynch IT, Abdelrahman AM, Alva-Ruiz R, et al. Cancer “Avatars”: patient-derived xenograft growth correlation with postoperative recurrence and survival in pancreaticobiliary cancer. J Am Coll Surg. 2023; 237(3): 483-500.

[7]

Chen Q, Wei T, Wang J, et al. Patient-derived xenograft model engraftment predicts poor prognosis after surgery in patients with pancreatic cancer. Pancreatology. 2020; 20(3): 485-492.

[8]

Nicolle R, Blum Y, Duconseil P, et al. Establishment of a pancreatic adenocarcinoma molecular gradient (PAMG) that predicts the clinical outcome of pancreatic cancer. EBioMedicine. 2020; 57: 102858.

[9]

Xu W, Yang XW, Zhao ZY, et al. Establishment of pancreatic cancer patient-derived xenograft models and comparison of the differences among the generations. Am J Transl Res. 2019; 11(5): 3128-3139.

[10]

Kumarasamy V, Ruiz A, Nambiar R, Witkiewicz AK, Knudsen ES. Chemotherapy impacts on the cellular response to CDK4/6 inhibition: distinct mechanisms of interaction and efficacy in models of pancreatic cancer. Oncogene. 2020; 39(9): 1831-1845.

[11]

Pauli C, Hopkins BD, Prandi D, et al. Personalized in vitro and in vivo cancer models to guide precision medicine. Cancer Discov. 2017; 7(5): 462-477.

[12]

Edsjö A, Holmquist L, Geoerger B, et al. Precision cancer medicine: concepts, current practice, and future developments. J Intern Med. 2023; 294(4): 455-481.

[13]

Li Y, Porta-Pardo E, Tokheim C, et al. Pan-cancer proteogenomics connects oncogenic drivers to functional states. Cell. 2023; 186(18): 3921-3944. e25.

[14]

Rygaard J, Povlsen CO. Heterotransplantation of a human malignant tumour to “Nude” mice. Acta Pathol Microbiol Scand. 1969; 77(4): 758-760.

[15]

Guillen KP, Fujita M, Butterfield AJ, et al. A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology. Nat Cancer. 2022; 3(2): 232-250.

[16]

Ouyang S, Li H, Lou L, et al. Inhibition of STAT3-ferroptosis negative regulatory axis suppresses tumor growth and alleviates chemoresistance in gastric cancer. Redox Biol. 2022; 52: 102317.

[17]

Sorokin AV, Kanikarla Marie P, Bitner L, et al. Targeting RAS mutant colorectal cancer with dual inhibition of MEK and CDK4/6. Cancer Res. 2022; 82(18): 3335-3344.

[18]

Torrini C, Nguyen TTT, Shu C, et al. Lactate is an epigenetic metabolite that drives survival in model systems of glioblastoma. Mol Cell. 2022; 82(16): 3061-3076.

[19]

Schuch LF, Silveira FM, Wagner VP, et al. Head and neck cancer patient-derived xenograft models—a systematic review. Crit Rev Oncol Hematol. 2020; 155: 103087.

[20]

Okada S, Vaeteewoottacharn K, Kariya R. Application of highly immunocompromised mice for the establishment of patient-derived xenograft (PDX) models. Cells. 2019; 8(8): 889.

[21]

Murayama T, Gotoh N. Patient-derived xenograft models of breast cancer and their application. Cells. 2019; 8(6): 621.

[22]

Dobrolecki LE, Airhart SD, Alferez DG, et al. Patient-derived xenograft (PDX) models in basic and translational breast cancer research. Cancer Metastasis Rev. 2016; 35(4): 547-573.

[23]

Wang Y, Wang JX, Xue H, et al. Subrenal capsule grafting technology in human cancer modeling and translational cancer research. Differentiation. 2016; 91(4-5): 15-19.

[24]

Giffin MJ, Cooke K, Lobenhofer EK, et al. AMG 757, a half-life extended, DLL3-targeted bispecific T-cell engager, shows high potency and sensitivity in preclinical models of small-cell lung cancer. Clin Cancer Res. 2021; 27(5): 1526-1537.

[25]

Budzynski W, Radzikowski C. Cytotoxic cells in immunodeficient athymic mice. Immunopharmacol Immunotoxicol. 1994; 16(3): 319-346.

[26]

Xie L, Shen M, Huang R, et al. Apoptosis of colon cancer CT-26 cells induced polysaccharide from Cyclocarya paliurus and its phosphorylated derivative via intrinsic mitochondrial passway. Food Sci Hum Wellness. 2023; 12(5): 1545-1556.

[27]

Yu X, Chen Y, Lu J, et al. Patient-derived xenograft models for gastrointestinal tumors: a single-center retrospective study. Front Oncol. 2022; 12: 985154.

[28]

Linnebacher M, Maletzki C, Ostwald C, et al. Cryopreservation of human colorectal carcinomas prior to xenografting. BMC Cancer. 2010; 10: 362.

[29]

Guenot D, Guérin E, Aguillon-Romain S, et al. Primary tumour genetic alterations and intra-tumoral heterogeneity are maintained in xenografts of human colon cancers showing chromosome instability. J Pathol. 2006; 208(5): 643-652.

[30]

Fichtner I, Slisow W, Gill J, et al. Anticancer drug response and expression of molecular markers in early-passage xenotransplanted colon carcinomas. Eur J Cancer. 2004; 40(2): 298-307.

[31]

Corso S, Isella C, Bellomo SE, et al. A comprehensive PDX gastric cancer collection captures cancer cell-intrinsic transcriptional MSI traits. Cancer Res. 2019; 79(22): 5884-5896.

[32]

Dangles-Marie V, Pocard M, Richon S, et al. Establishment of human colon cancer cell lines from fresh tumors versus xenografts: comparison of success rate and cell line features. Cancer Res. 2007; 67(1): 398-407.

[33]

Yu Y-Y, Duan Y-N, Ma S, Hu Q-H, Ma G-X. Research progress on the mechanism of functional activity of edible fungi polysaccharides—focusing intestinal mucus as a key and entry point. Food Med Homol. 2025; 2(1): 9420042.

[34]

Tentler JJ, Tan AC, Weekes CD, et al. Patient-derived tumour xenografts as models for oncology drug development. Nat Rev Clin Oncol. 2012; 9(6): 338-350.

[35]

Cutz JC, Guan J, Bayani J, et al. Establishment in severe combined immunodeficiency mice of subrenal capsule xenografts and transplantable tumor lines from a variety of primary human lung cancers: potential models for studying tumor progression-related changes. Clin Cancer Res. 2006; 12(13): 4043-4054.

[36]

Coppin C, Kollmannsberger C, Le L, Porzsolt F, Wilt TJ. Targeted therapy for advanced renal cell cancer (RCC): a Cochrane systematic review of published randomised trials. BJU Int. 2011; 108(10): 1556-1563.

[37]

Dong X, Guan J, English JC, et al. Patient-derived first generation xenografts of non-small cell lung cancers: promising tools for predicting drug responses for personalized chemotherapy. Clin Cancer Res. 2010; 16(5): 1442-1451.

[38]

Fichtner I, Rolff J, Soong R, et al. Establishment of patient-derived non-small cell lung cancer xenografts as models for the identification of predictive biomarkers. Clin Cancer Res. 2008; 14(20): 6456-6468.

[39]

Moro M, Bertolini G, Tortoreto M, Pastorino U, Sozzi G, Roz L. Patient-derived xenografts of non small cell lung cancer: resurgence of an old model for investigation of modern concepts of tailored therapy and cancer stem cells. J Biomed Biotechnol. 2012; 2012: 568567.

[40]

DiPeri TP, Evans KW, Wang B, et al. Co-clinical trial of novel bispecific anti-HER2 antibody zanidatamab in patient-derived xenografts. Cancer Discov. 2024; 14(5): 828-845.

[41]

Serra-Camprubí Q, Verdaguer H, Oliveros W, et al. Human metastatic cholangiocarcinoma patient-derived xenografts and tumoroids for preclinical drug evaluation. Clin Cancer Res. 2023; 29(2): 432-445.

[42]

Risbridger GP, Clark AK, Porter LH, et al. The MURAL collection of prostate cancer patient-derived xenografts enables discovery through preclinical models of uro-oncology. Nat Commun. 2021; 12(1): 5049.

[43]

Bonazzi VF, Kondrashova O, Smith D, et al. Patient-derived xenograft models capture genomic heterogeneity in endometrial cancer. Genome Med. 2022; 14(1): 3.

[44]

Echeverria GV, Cai S, Tu Y, et al. Predictors of success in establishing orthotopic patient-derived xenograft models of triple negative breast cancer. NPJ Breast Cancer. 2023; 9(1): 2.

[45]

Hynds RE, Huebner A, Pearce DR, et al. Representation of genomic intratumor heterogeneity in multi-region non-small cell lung cancer patient-derived xenograft models. Nat Commun. 2024; 15(1): 4653.

[46]

Jiang Y, Zhao J, Zhang Y, et al. Establishment of lung cancer patient-derived xenograft models and primary cell lines for lung cancer study. J Transl Med. 2018; 16(1): 138.

[47]

Bu J, Zhang Y, Wu S, et al. KK-LC-1 as a therapeutic target to eliminate ALDH(+) stem cells in triple negative breast cancer. Nat Commun. 2023; 14(1): 2602.

[48]

Min C, Moore N, Shearstone JR, et al. Selective inhibitors of histone deacetylases 1 and 2 synergize with azacitidine in acute myeloid leukemia. PLoS One. 2017; 12(1): e0169128.

[49]

Passaro D, Di Tullio A, Abarrategi A, et al. Increased vascular permeability in the bone marrow microenvironment contributes to disease progression and drug response in acute myeloid leukemia. Cancer Cell. 2017; 32(3): 324-341.

[50]

Sun M, Wang Z, Sun W, et al. Correlation between patient-derived xenograft modeling and prognosis in osteosarcoma. Orthop Surg. 2022; 14(6): 1161-1166.

[51]

Ohkuma R, Yada E, Ishikawa S, et al. High expression of olfactomedin-4 is correlated with chemoresistance and poor prognosis in pancreatic cancer. PLoS One. 2020; 15(1): e0226707.

[52]

Wang J, Miletic H, Sakariassen P, et al. A reproducible brain tumour model established from human glioblastoma biopsies. BMC Cancer. 2009; 9: 465.

[53]

DeRose YS, Wang G, Lin YC, et al. Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes. Nat Med. 2011; 17(11): 1514-1520.

[54]

Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000; 92(3): 205-216.

[55]

Gao H, Korn JM, Ferretti S, et al. High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response. Nat Med. 2015; 21(11): 1318-1325.

[56]

Wang Z, Fu S, Zhao J, et al. Transbronchoscopic patient biopsy-derived xenografts as a preclinical model to explore chemorefractory-associated pathways and biomarkers for small-cell lung cancer. Cancer Lett. 2019; 440-441: 180-188.

[57]

Drapkin BJ, George J, Christensen CL, et al. Genomic and functional fidelity of small cell lung cancer patient-derived xenografts. Cancer Discov. 2018; 8(5): 600-615.

[58]

Norton JP, Augert A, Eastwood E, Basom R, Rudin CM, MacPherson D. Protein neddylation as a therapeutic target in pulmonary and extrapulmonary small cell carcinomas. Genes Dev. 2021; 35(11-12): 870-887.

[59]

Suvilesh KN, Nussbaum YI, Radhakrishnan V, et al. Tumorigenic circulating tumor cells from xenograft mouse models of non-metastatic NSCLC patients reveal distinct single cell heterogeneity and drug responses. Mol Cancer. 2022; 21(1): 73.

[60]

Mou X, Zhang A, He T, et al. Organoid models for Chinese herbal medicine studies. J Acta Materia Medica. 2023; 2(1): 64-71.

[61]

Romero-Calvo I, Weber CR, Ray M, et al. Human organoids share structural and genetic features with primary pancreatic adenocarcinoma tumors. Mol Cancer Res. 2019; 17(1): 70-83.

[62]

Hidalgo M, Amant F, Biankin AV, et al. Patient-derived xenograft models: an emerging platform for translational cancer research. Cancer Discov. 2014; 4(9): 998-1013.

[63]

Blomme A, Van Simaeys G, Doumont G, et al. Murine stroma adopts a human-like metabolic phenotype in the PDX model of colorectal cancer and liver metastases. Oncogene. 2018; 37(9): 1237-1250.

[64]

Yoshida GJ. Applications of patient-derived tumor xenograft models and tumor organoids. J Hematol Oncol. 2020; 13(1): 4.

[65]

Mosmann TR, Yokota T, Kastelein R, Zurawski SM, Arai N, Takebe Y. Species-specificity of T cell stimulating activities of IL 2 and BSF-1 (IL 4): comparison of normal and recombinant, mouse and human IL 2 and BSF-1 (IL 4). J Immunol. 1987; 138(6): 1813-1816.

[66]

Eisenman J, Ahdieh M, Beers C, et al. Interleukin-15 interactions with interleukin-15 receptor complexes: characterization and species specificity. Cytokine. 2002; 20(3): 121-129.

[67]

Zhan M, Huo R, Zhu B, Zhi Q. Annual advances of traditional Chinese medicine on tumor immunity regulation in 2021. Tradit Med Res. 2022; 7(6): 56.

[68]

Pu X, Zhang R, Wang L, et al. Patient-derived tumor immune microenvironments in patient-derived xenografts of lung cancer. J Transl Med. 2018; 16(1): 328.

[69]

Su L, Fang M-H, Zou J, et al. Posttransplant blockade of CXCR4 improves leukemia complete remission rates and donor stem cell engraftment without aggravating GVHD. Cell Mol Immunol. 2021; 18(11): 2541-2553.

[70]

Chen S-W, Zhu S-Q, Pei X, et al. Cancer cell-derived exosomal circUSP7 induces CD8+ T cell dysfunction and anti-PD1 resistance by regulating the miR-934/SHP2 axis in NSCLC. Mol Cancer. 2021; 20(1): 144.

[71]

Meraz IM, Majidi M, Meng F, et al. An improved patient-derived xenograft humanized mouse model for evaluation of lung cancer immune responses. Cancer Immunol Res. 2019; 7(8): 1267-1279.

[72]

Chiorazzi M, Martinek J, Krasnick B, et al. Autologous humanized PDX modeling for immuno-oncology recapitulates features of the human tumor microenvironment. J Immunother Cancer. 2023; 11(7): e006921.

[73]

Hoge ACH, Getz M, Zimmer A, et al. DNA-based copy number analysis confirms genomic evolution of PDX models. NPJ Precis Oncol. 2022; 6(1): 30.

[74]

Sprouffske K, Kerr G, Li C, et al. Genetic heterogeneity and clonal evolution during metastasis in breast cancer patient-derived tumor xenograft models. Comput Struct Biotechnol J. 2020; 18: 323-331.

[75]

Gu A, Li J, Wu J-A, Li M-Y, Liu Y. Exploration of Dan-Shen-Yin against pancreatic cancer based on network pharmacology combined with molecular docking and experimental validation. Curr Res Biotechnol. 2024; 7: 100228.

[76]

Yang Y, Guan S, Ou Z, Li W, Yan L, Situ B. Advances in AI-based cancer cytopathology. Interdiscip Med. 2023; 1(3): e20230013.

[77]

Wirth AK, Wange L, Vosberg S, et al. In vivo PDX CRISPR/Cas9 screens reveal mutual therapeutic targets to overcome heterogeneous acquired chemo-resistance. Leukemia. 2022; 36(12): 2863-2874.

[78]

Zhang X, Yu K, Ma L, et al. Endogenous glutamate determines ferroptosis sensitivity via ADCY10-dependent YAP suppression in lung adenocarcinoma. Theranostics. 2021; 11(12): 5650-5674.

[79]

Cai S, Li N, Bai X, et al. ERK inactivation enhances stemness of NSCLC cells via promoting Slug-mediated epithelial-to-mesenchymal transition. Theranostics. 2022; 12(16): 7051-7066.

[80]

Noronha A, Belugali Nataraj N, Lee JS, et al. AXL and error-prone DNA replication confer drug resistance and offer strategies to treat EGFR-mutant lung cancer. Cancer Discov. 2022; 12(11): 2666-2683.

[81]

Woo XY, Srivastava A, Mack PC, et al. A genomically and clinically annotated patient-derived xenograft resource for preclinical research in non-small cell lung cancer. Cancer Res. 2022; 82(22): 4126-4138.

[82]

Saad MI, Alhayyani S, McLeod L, et al. ADAM17 selectively activates the IL-6 trans-signaling/ERK MAPK axis in KRAS-addicted lung cancer. EMBO Mol Med. 2019; 11(4): e9976.

[83]

Pan Y, Han H, Hu H, et al. KMT2D deficiency drives lung squamous cell carcinoma and hypersensitivity to RTK-RAS inhibition. Cancer Cell. 2023; 41(1): 88-105.

[84]

Gao L, Hu Y, Tian Y, et al. Lung cancer deficient in the tumor suppressor GATA4 is sensitive to TGFBR1 inhibition. Nat Commun. 2019; 10(1): 1665.

[85]

Liu Q, Zhang J, Guo C, et al. Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies. Cell. 2024; 187(1): 184-203.

[86]

Zhan J, Wang P, Li S, et al. HOXB13 networking with ABCG1/EZH2/Slug mediates metastasis and confers resistance to cisplatin in lung adenocarcinoma patients. Theranostics. 2019; 9(7): 2084-2099.

[87]

Grunblatt E, Wu N, Zhang H, et al. MYCN drives chemoresistance in small cell lung cancer while USP7 inhibition can restore chemosensitivity. Genes Dev. 2020; 34(17-18): 1210-1226.

[88]

Qian Y, Shi C, Cheng C, Liao D, Liu J, Chen G-T. Ginger polysaccharide UGP1 suppressed human colon cancer growth via p53, Bax/Bcl-2, caspase-3 pathways and immunomodulation. Food Sci Hum Wellness. 2023; 12(2): 467-476.

[89]

Kong N, Ma H, Pu Z, et al. De novo design and synthesis of polypeptide immunomodulators for resetting macrophage polarization. BioDesign Res. 2023; 5: 0006.

[90]

Mountzios G, Remon J, Hendriks LEL, et al. Immune-checkpoint inhibition for resectable non-small-cell lung cancer—opportunities and challenges. Nat Rev Clin Oncol. 2023; 20(10): 664-677.

[91]

Lu Y, Zeng T, Zhang H, et al. Nano-immunotherapy for lung cancer. Nano TransMed. 2023; 2(1): e9130018.

[92]

Saad MB, Hong L, Aminu M, et al. Predicting benefit from immune checkpoint inhibitors in patients with non-small-cell lung cancer by CT-based ensemble deep learning: a retrospective study. Lancet Digit Health. 2023; 5(7): e404-e420.

[93]

Lin R, Zhang H, Yuan Y, et al. Fatty acid oxidation controls CD8(+) tissue-resident memory T-cell survival in gastric adenocarcinoma. Cancer Immunol Res. 2020; 8(4): 479-492.

[94]

Zhou Z, Li X, Yang G, et al. Targeting β-catenin and PD-L1 simultaneously by a racemic supramolecular peptide for the potent immunotherapy of hepatocellular carcinoma. Theranostics. 2023; 13(10): 3371-3386.

[95]

Anobile DP, Salaroglio IC, Tabbò F, et al. Autocrine 17-β-estradiol/estrogen receptor-α loop determines the response to immune checkpoint inhibitors in non-small cell lung cancer. Clin Cancer Res. 2023; 29(19): 3958-3973.

[96]

Cheson BD, Nowakowski G, Salles G. Diffuse large B-cell lymphoma: new targets and novel therapies. Blood Cancer J. 2021; 11(4): 68.

[97]

Flugel CL, Majzner RG, Krenciute G, et al. Overcoming on-target, off-tumour toxicity of CAR T cell therapy for solid tumours. Nat Rev Clin Oncol. 2023; 20(1): 49-62.

[98]

Cao B, Liu M, Wang L, et al. Remodelling of tumour microenvironment by microwave ablation potentiates immunotherapy of AXL-specific CAR T cells against non-small cell lung cancer. Nat Commun. 2022; 13(1): 6203.

[99]

Mu Z, Tran B-M, Xu H, et al. Exploring the potential application of coconut water in healthcare and biotechnology: a review. Beverage Plant Res. 2024; 4(1): e018.

[100]

Chen Y-H, Xu H, Hu D, et al. Traditional medicine in cancer: what is new in 2022. Tradit Med Res. 2023; 8: 43-48.

[101]

Zou X, Liu H. A review of meroterpenoids and of their bioactivity from guava (Psidium guajava L.). J Future Foods. 2023; 3(2): 142-154.

[102]

Liu Y, Bian Y, Bai Y, et al. Potato protease inhibitors, a functional food material with antioxidant and anticancer potential. Food Sci Hum Wellness. 2023; 12(5): 1762-1771.

[103]

Li J, Gu A, Li M-Y. Heteroaryl group containing trisubstituted alkenes: synthesis and anti-tumor activity. Chem Biodivers. 2024; 21(11): e202401469.

[104]

Li J, Gu A, Nong X-M, et al. Six-membered aromatic nitrogen heterocyclic anti-tumor agents: synthesis and applications. Chem Rec. 2023; 23(12): e202300293.

[105]

Majeed S, Aparnathi MK, Nixon KCJ, et al. Targeting the ubiquitin–proteasome system using the UBA1 inhibitor TAK-243 is a potential therapeutic strategy for small-cell lung cancer. Clin Cancer Res. 2022; 28(9): 1966-1978.

[106]

Xiao W, Ma W, Wei S, et al. High-affinity peptide ligand LXY30 for targeting α3β1 integrin in non-small cell lung cancer. J Hematol Oncol. 2019; 12(1): 56.

[107]

Pan Q, Zhong S, Wang H, et al. The ZMYND8-regulated mevalonate pathway endows YAP-high intestinal cancer with metabolic vulnerability. Mol Cell. 2021; 81(13): 2736-2751.

[108]

Mullen PJ, Yu R, Longo J, Archer MC, Penn LZ. The interplay between cell signalling and the mevalonate pathway in cancer. Nat Rev Cancer. 2016; 16(11): 718-731.

[109]

Ni W, Mo H, Liu Y, et al. Targeting cholesterol biosynthesis promotes anti-tumor immunity by inhibiting long noncoding RNA SNHG29-mediated YAP activation. Mol Ther. 2021; 29(10): 2995-3010.

[110]

Wu H, Wan J, Yuan J, et al. Neuroprotective comparisons and bioactive profiles of green tea and black tea: in vitro cellular experiments, metabolomics, and network pharmacology analysis. Beverage Plant Res. 2024; 4(1): e017.

[111]

Ye X-S, Tian W-J, Wang G-H, et al. The food and medicine homologous Chinese Medicine from Leguminosae species: a comprehensive review on bioactive constituents with neuroprotective effects on nervous system. Food Med Homol. 2025; 2(2): 9420033.

[112]

Qu J, Qiu B, Zhang Y, et al. The tumor-enriched small molecule gambogic amide suppresses glioma by targeting WDR1-dependent cytoskeleton remodeling. Signal Transduct Target Ther. 2023; 8(1): 424.

[113]

Fan Y, Wang W, Wang X, et al. Ganoderma lucidum polysaccharide inhibits LPS-induced inflammatory injury to mammary epithelial cells. J Future Foods. 2023; 3(1): 49-54.

[114]

Echeverria GV, Ge Z, Seth S, et al. Resistance to neoadjuvant chemotherapy in triple-negative breast cancer mediated by a reversible drug-tolerant state. Sci Transl Med. 2019; 11(488): eaav0936.

[115]

Navarro-Yepes J, Kettner NM, Rao X, et al. Abemaciclib is effective in palbociclib-resistant hormone receptor–positive metastatic breast cancers. Cancer Res. 2023; 83(19): 3264-3283.

[116]

Khersonsky O, Fleishman SJ. What have we learned from design of function in large proteins?. BioDesign Res. 2022; 2022: 9787581.

[117]

Melesse Vergara M, Labbé J, Tannous J. Reflection on the challenges, accomplishments, and new frontiers of gene drives. BioDesign Res. 2022; 2022: 9853416.

[118]

Krivtsov AV, Evans K, Gadrey JY, et al. A menin-MLL inhibitor induces specific chromatin changes and eradicates disease in models of MLL-rearranged leukemia. Cancer Cell. 2019; 36(6): 660-673.

[119]

Yuan M, Huang LL, Chen JH, Wu J, Xu Q. The emerging treatment landscape of targeted therapy in non-small-cell lung cancer. Signal Transd Target Ther. 2019; 4: 61.

[120]

Robichaux JP, Le X, Vijayan RSK, et al. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature. 2021; 597(7878): 732-737.

[121]

Melosky B, Kambartel K, Häntschel M, et al. Worldwide prevalence of epidermal growth factor receptor mutations in non-small cell lung cancer: a meta-analysis. Mol Diagn Ther. 2022; 26(1): 7-18.

[122]

Robichaux JP, Elamin YY, Tan Z, et al. Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer. Nat Med. 2018; 24(5): 638-646.

[123]

Elamin YY, Robichaux JP, Carter BW, et al. Poziotinib for EGFR exon 20-mutant NSCLC: clinical efficacy, resistance mechanisms, and impact of insertion location on drug sensitivity. Cancer Cell. 2022; 40(7): 754-767.

[124]

Gonzalvez F, Vincent S, Baker TE, et al. Mobocertinib (TAK-788): a targeted inhibitor of EGFR exon 20 insertion mutants in non–small cell lung cancer. Cancer Discov. 2021; 11(7): 1672-1687.

[125]

Han H, Li S, Chen T, et al. Targeting HER2 exon 20 insertion–mutant lung adenocarcinoma with a novel tyrosine kinase inhibitor mobocertinib. Cancer Res. 2021; 81(20): 5311-5324.

[126]

Yun J, Lee S-H, Kim S-Y, et al. Antitumor activity of amivantamab (JNJ-61186372), an EGFR–MET bispecific antibody, in diverse models of EGFR exon 20 insertion–driven NSCLC. Cancer Discov. 2020; 10(8): 1194-1209.

[127]

Floc’h N, Lim S, Bickerton S, et al. Osimertinib, an irreversible next-generation EGFR tyrosine kinase inhibitor, exerts antitumor activity in various preclinical nsclc models harboring the uncommon EGFR mutations G719X or L861Q or S768I. Mol Cancer Ther. 2020; 19(11): 2298-2307.

[128]

Tian X, Wang R, Gu T, et al. Costunolide is a dual inhibitor of MEK1 and AKT1/2 that overcomes osimertinib resistance in lung cancer. Mol Cancer. 2022; 21(1): 193.

[129]

Lim SM, Fujino T, Kim C, et al. BBT-176, a novel fourth-generation tyrosine kinase inhibitor for osimertinib-resistant EGFR mutations in non–small cell lung cancer. Clin Cancer Res. 2023; 29(16): 3004-3016.

[130]

Marrocco I, Romaniello D, Vaknin I, et al. Upfront admixing antibodies and EGFR inhibitors preempts sequential treatments in lung cancer models. EMBO Mol Med. 2021; 13(4): e13144.

[131]

Zhang KR, Zhang YF, Lei HM, et al. Targeting AKR1B1 inhibits glutathione de novo synthesis to overcome acquired resistance to EGFR-targeted therapy in lung cancer. Sci Transl Med. 2021; 13(614): eabg6428.

[132]

Shigematsu H, Takahashi T, Nomura M, et al. Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res. 2005; 65(5): 1642-1646.

[133]

Buttitta F, Barassi F, Fresu G, et al. Mutational analysis of the HER2 gene in lung tumors from Caucasian patients: mutations are mainly present in adenocarcinomas with bronchioloalveolar features. Int J Cancer. 2006; 119(11): 2586-2591.

[134]

Kris MG, Johnson BE, Berry LD, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014; 311(19): 1998-2006.

[135]

Wang Y, Jiang T, Qin Z, et al. HER2 exon 20 insertions in non-small-cell lung cancer are sensitive to the irreversible pan-HER receptor tyrosine kinase inhibitor pyrotinib. Ann Oncol. 2019; 30(3): 447-455.

[136]

Recondo G, Mezquita L, Facchinetti F, et al. Diverse resistance mechanisms to the third-generation ALK inhibitor lorlatinib in ALK-rearranged lung cancer. Clin Cancer Res. 2020; 26(1): 242-255.

[137]

Fang DD, Zhang B, Gu Q, et al. HIP1-ALK, a novel ALK fusion variant that responds to crizotinib. J Thorac Oncol. 2014; 9(3): 285-294.

[138]

Rosti G, Castagnetti F, Gugliotta G, Baccarani M. Tyrosine kinase inhibitors in chronic myeloid leukaemia: which, when, for whom?. Nat Rev Clin Oncol. 2017; 14(3): 141-154.

[139]

Garmendia I, Pajares MJ, Hermida-Prado F, et al. YES1 drives lung cancer growth and progression and predicts sensitivity to dasatinib. Am J Respir Crit Care Med. 2023; 200(7): 888–899.

[140]

Redin E, Garrido-Martin EM, Valencia K, et al. YES1 is a druggable oncogenic target in SCLC. J Thorac Oncol. 2022; 17(12): 1387-1403.

[141]

Wang N, Zhao Q, Huang Y, et al. Lnc-TMEM132D-AS1 as a potential therapeutic target for acquired resistance to osimertinib in non-small-cell lung cancer. Mol Omics. 2023; 19(3): 238-251.

[142]

Petty WJ, Paz-Ares L. Emerging strategies for the treatment of small cell lung cancer: a review. JAMA Oncol. 2023; 9(3): 419-429.

[143]

Wang H, Yuan S, Zheng Q, et al. Dual inhibition of CDK4/6 and XPO1 induces senescence with acquired vulnerability to CRBN-based PROTAC drugs. Gastroenterology. 2024; 166(6): 1130-1144.

[144]

Lakhani NJ, Rasco D, Wang H, et al. First-in-human study with preclinical data of BCL-2/BCL-xL inhibitor pelcitoclax in locally advanced or metastatic solid tumors. Clin Cancer Res. 2024; 30(3): 506-521.

[145]

Xu Y, Gu L, Li Y, et al. Integrative genomic analysis of drug resistance in MET exon 14 skipping lung cancer using patient-derived xenograft models. Front Oncol. 2022; 12: 1024818.

[146]

Schram AM, Odintsov I, Espinosa-Cotton M, et al. Zenocutuzumab, a HER2xHER3 bispecific antibody, is effective therapy for tumors driven by NRG1 gene rearrangements. Cancer Discov. 2022; 12(5): 1233-1247.

[147]

Maes T, Mascaró C, Tirapu I, et al. ORY-1001, a potent and selective covalent KDM1A inhibitor, for the treatment of acute leukemia. Cancer Cell. 2018; 33(3): 495-511.

[148]

Chen M, Sun Y, Liu H. Cell membrane biomimetic nanomedicines for cancer phototherapy. Interdiscip Med. 2023; 1(2): e20220012.

[149]

Xue J, Luo Y. Protein-polysaccharide nanocomplexes as nanocarriers for delivery of curcumin: a comprehensive review on preparation methods and encapsulation mechanisms. J Future Foods. 2023; 3(2): 99-114.

[150]

Wang J, Liao Z-X. Research progress of microrobots in tumor drug delivery. Food Med Homol. 2024; 1(2): 9420025.

[151]

Chen W. On nano-solutions to overcome cancer hypoxia and resistance. Nano TransMed. 2023; 2(1): e9130020.

[152]

Wang C, Wang Y, Tian W, et al. Application of nanomaterials with sulfur vacancy for enhanced cancer theranostics. Nano TransMed. 2023; 2(2): 100007.

[153]

Zhang F, Hu Q, Li B, et al. A biomimetic nanodrug for enhanced chemotherapy of pancreatic tumors. J Control Release. 2023; 354: 835-850.

[154]

Zhang M, Ye L, Huang H, et al. Micelles self-assembled by 3-O-β-D-glucopyranosyl latycodigenin enhance cell membrane permeability, promote antibiotic pulmonary targeting and improve anti-infective efficacy. J Nanobiotechnol. 2020; 18(1): 140.

[155]

Cao P, Zhang Q, Wu S, et al. Baseline differences in metabolic profiles of patients with lung squamous cell carcinoma responding or not responding to treatment with nanoparticle albumin-bound paclitaxel (nab-paclitaxel). Acta Mater Med. 2023; 2(3): 347-356.

[156]

Tsai LL, Fitzgerald DM, Liu R, et al. Porous paclitaxel mesh reduces local recurrence in patient-derived xenograft resection model. Ann Thorac Surg. 2023; 116(1): 181-188.

[157]

Wang L, Fu H, Song L, et al. Overcoming AZD9291 resistance and metastasis of NSCLC via ferroptosis and multitarget interference by nanocatalytic sensitizer plus AHP-DRI-12. Small. 2022; 19(4): e2204133.

[158]

Mulay AR, Hwang J, Kim DH. Microphysiological blood-brain barrier systems for disease modeling and drug development. Adv Healthc Mater. 2024; 13(21): e2303180.

[159]

Zhan Q, Yi K, Cui X, et al. Blood exosomes-based targeted delivery of cPLA2 siRNA and metformin to modulate glioblastoma energy metabolism for tailoring personalized therapy. Neuro Oncol. 2022; 24(11): 1871-1883.

[160]

Stanzione M, Zhong J, Wong E, et al. Translesion DNA synthesis mediates acquired resistance to olaparib plus temozolomide in small cell lung cancer. Sci Adv. 2022; 8(19): eabn1229.

[161]

DiPeri TP, Evans KW, Raso MG, et al. Adavosertib enhances antitumor activity of trastuzumab deruxtecan in HER2-expressing cancers. Clin Cancer Res. 2023; 29(21): 4385-4398.

[162]

Tucker ER, Jiménez I, Chen L, et al. Combination therapies targeting ALK-aberrant neuroblastoma in preclinical models. Clin Cancer Res. 2023; 29(7): 1317-1331.

[163]

Gürgen D, Conrad T, Becker M, et al. Breaking the crosstalk of the cellular tumorigenic network by low-dose combination therapy in lung cancer patient-derived xenografts. Commun Biol. 2022; 5(1): 59.

[164]

Tang KH, Li S, Khodadadi-Jamayran A, et al. Combined inhibition of SHP2 and CXCR1/2 promotes antitumor T-cell response in NSCLC. Cancer Discov. 2022; 12(1): 47-61.

[165]

Elkrief A, Odintsov I, Markov V, et al. Combination therapy with MDM2 and MEK inhibitors is effective in patient-derived models of lung adenocarcinoma with concurrent oncogenic drivers and MDM2 amplification. J Thorac Oncol. 2023; 18(9): 1165-1183.

[166]

Kendsersky NM, Lindsay J, Kolb EA, et al. The B7-H3-targeting antibody-drug conjugate m276-SL-PBD is potently effective against pediatric cancer preclinical solid tumor models. Clin Cancer Res. 2021; 27(10): 2938-2946.

[167]

Geng Y, Chen S, Yang Y, et al. Long-term exposure to genistein inhibits the proliferation of gallbladder cancer by downregulating the MCM complex. Sci Bull (Beijing). 2022; 67(8): 813-824.

[168]

Liu H, Chen X, Jia Y, et al. Facing inevitable PARPis resistance: mechanisms and therapeutic strategies for breast cancer treatment. Interdiscip Med. 2023; 1(2): e20220013.

[169]

Strickler JH, Yoshino T, Graham RP, Siena S, Bekaii-Saab T. Diagnosis and treatment of ERBB2-positive metastatic colorectal cancer: a review. JAMA Oncol. 2022; 8(5): 760-769.

[170]

Wolff AC, Somerfield MR, Dowsett M, et al. Human epidermal growth factor receptor 2 testing in breast cancer: ASCO-College of American Pathologists Guideline Update. J Clin Oncol. 2023; 41(22): 3867-3872.

[171]

Odintsov I, Makarem M, Nishino M, et al. Prevalence and therapeutic targeting of high-level ERBB2 amplification in NSCLC. J Thorac Oncol. 2024; 19(5): 732-748.

[172]

Shih CH, Lin YH, Luo HL, Sung WW. Antibody-drug conjugates targeting HER2 for the treatment of urothelial carcinoma: potential therapies for HER2-positive urothelial carcinoma. Front Pharmacol. 2024; 15: 1326296.

[173]

Choi J, Ko EJ, Ju EJ, et al. Characterization of sphere cells derived from a patient-derived xenograft model of lung adenocarcinoma treated with ionizing radiation. Int J Radiat Biol. 2020; 96(11): 1413-1422.

[174]

Tully KM, Tendler S, Carter LM, et al. Radioimmunotherapy targeting delta-like ligand 3 in small cell lung cancer exhibits antitumor efficacy with low toxicity. Clin Cancer Res. 2022; 28(7): 1391-1401.

[175]

Pereira C, Gimenez-Xavier P, Pros E, et al. Genomic profiling of patient-derived xenografts for lung cancer identifies B2M inactivation impairing immunorecognition. Clin Cancer Res. 2017; 23(12): 3203-3213.

[176]

Hoppe MM, Jaynes P, Shuangyi F, et al. Patterns of oncogene coexpression at single-cell resolution influence survival in lymphoma. Cancer Discov. 2023; 13(5): 1144-1163.

[177]

Bahrami E, Schmid JP, Jurinovic V, et al. Combined proteomics and CRISPR–Cas9 screens in PDX identify ADAM10 as essential for leukemia in vivo. Mol Cancer. 2023; 22(1): 107.

[178]

Zeller C, Richter D, Jurinovic V, et al. Adverse stem cell clones within a single patient’s tumor predict clinical outcome in AML patients. J Hematol Oncol. 2022; 15(1): 25.

[179]

Ramkumar K, Tanimoto A, Della Corte CM, et al. Targeting BCL2 overcomes resistance and augments response to aurora kinase B inhibition by AZD2811 in small cell lung cancer. Clin Cancer Res. 2023; 29(16): 3237-3249.

[180]

Zhao Y, Murciano-Goroff YR, Xue JY, et al. Diverse alterations associated with resistance to KRAS(G12C) inhibition. Nature. 2021; 599(7886): 679-683.

[181]

Quintanal-Villalonga A, Taniguchi H, Zhan YA, et al. Comprehensive molecular characterization of lung tumors implicates AKT and MYC signaling in adenocarcinoma to squamous cell transdifferentiation. J Hematol Oncol. 2021; 14(1): 170.

[182]

Cejas P, Xie Y, Font-Tello A, et al. Subtype heterogeneity and epigenetic convergence in neuroendocrine prostate cancer. Nat Commun. 2021; 12(1): 5775.

[183]

Sun H, Cao S, Mashl RJ, et al. Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidates for targeted treatment. Nat Commun. 2021; 12(1): 5086.

[184]

Mirhadi S, Tam S, Li Q, et al. Integrative analysis of non-small cell lung cancer patient-derived xenografts identifies distinct proteotypes associated with patient outcomes. Nat Commun. 2022; 13(1): 1811.

[185]

Lissa D, Takahashi N, Desai P, et al. Heterogeneity of neuroendocrine transcriptional states in metastatic small cell lung cancers and patient-derived models. Nat Commun. 2022; 13(1): 2023.

[186]

Caeser R, Egger JV, Chavan S, et al. Genomic and transcriptomic analysis of a library of small cell lung cancer patient-derived xenografts. Nat Commun. 2022; 13(1): 2144.

[187]

Quintanal-Villalonga A, Taniguchi H, Zhan YA, et al. Multiomic analysis of lung tumors defines pathways activated in neuroendocrine transformation. Cancer Discov. 2021; 11(12): 3028-3047.

[188]

Tedesco M, Giannese F, Lazarević D, et al. Chromatin Velocity reveals epigenetic dynamics by single-cell profiling of heterochromatin and euchromatin. Nat Biotechnol. 2022; 40(2): 235-244.

[189]

Panovska D, Nazari P, Cole B, et al. Single-cell molecular profiling using ex vivo functional readouts fuels precision oncology in glioblastoma. Cell Mol Life Sci. 2023; 80(6): 147.

[190]

She C, Wu C, Guo W, et al. Combination of RUNX1 inhibitor and gemcitabine mitigates chemo-resistance in pancreatic ductal adenocarcinoma by modulating BiP/PERK/eIF2α-axis-mediated endoplasmic reticulum stress. J Exp Clin Cancer Res. 2023; 42(1): 238.

[191]

Wu Y, Chen S, Yang X, et al. Combining the tyrosine kinase inhibitor cabozantinib and the mTORC1/2 inhibitor sapanisertib blocks ERK pathway activity and suppresses tumor growth in renal cell carcinoma. Cancer Res. 2023; 83(24): 4161-4178.

[192]

Chen J, Facchinetti F, Braye F, et al. Single-cell DNA-seq depicts clonal evolution of multiple driver alterations in osimertinib-resistant patients. Ann Oncol. 2022; 33(4): 434-444.

[193]

Moghal N, Li Q, Stewart EL, et al. Single-cell analysis reveals transcriptomic features of drug-tolerant persisters and stromal adaptation in a patient-derived EGFR-mutated lung adenocarcinoma xenograft model. J Thorac Oncol. 2023; 18(4): 499-515.

[194]

Kim KT, Lee HW, HO Lee, et al. Single-cell mRNA sequencing identifies subclonal heterogeneity in anti-cancer drug responses of lung adenocarcinoma cells. Genome Biol. 2015; 16(1): 127.

[195]

Yoshitake R, Mori H, Ha D, et al. Molecular features of luminal breast cancer defined through spatial and single-cell transcriptomics. Clin Transl Med. 2024; 14(1): e1548.

[196]

Kabeer F, Tran H, Andronescu M, et al. Single-cell decoding of drug induced transcriptomic reprogramming in triple negative breast cancers. Genome Biol. 2024; 25(1): 191.

[197]

Stewart CA, Gay CM, Xi Y, et al. Single-cell analyses reveal increased intratumoral heterogeneity after the onset of therapy resistance in small-cell lung cancer. Nat Cancer. 2020; 1(4): 423-436.

[198]

Evrard YA, Srivastava A, Randjelovic J, et al. Systematic establishment of robustness and standards in patient-derived xenograft experiments and analysis. Cancer Res. 2020; 80(11): 2286-2297.

[199]

Hunter AM, Newman H, Dezern AE, et al. Integrated human and murine clinical study establishes clinical efficacy of ruxolitinib in chronic myelomonocytic leukemia. Clin Cancer Res. 2021; 27(22): 6095-6105.

[200]

Kim HR, Kang HN, Shim HS, et al. Co-clinical trials demonstrate predictive biomarkers for dovitinib, an FGFR inhibitor, in lung squamous cell carcinoma. Ann Oncol. 2017; 28(6): 1250-1259.

[201]

DiPeri TP, Evans KW, Wang B, et al. Co-clinical trial of novel bispecific anti-HER2 antibody zanidatamab in patient-derived xenografts. Cancer Discov. 2024; 14(5): 828-845.

[202]

Lopez BGC, Kohale IN, Du Z, et al. Multimodal platform for assessing drug distribution and response in clinical trials. Neuro-oncol. 2022; 24(1): 64-77.

[203]

Townsend EC, Murakami MA, Christodoulou A, et al. The public repository of xenografts enables discovery and randomized phase II-like trials in mice. Cancer Cell. 2016; 29(4): 574-586.

[204]

Murphy B, Yin H, Maris JM, et al. Evaluation of alternative in vivo drug screening methodology: a single mouse analysis. Cancer Res. 2016; 76(19): 5798-5809.

[205]

Yao Y, Wang Y, Chen L, et al. Clinical utility of PDX cohorts to reveal biomarkers of intrinsic resistance and clonal architecture changes underlying acquired resistance to cetuximab in HNSCC. Signal Transduct Target Ther. 2022; 7(1): 73.

[206]

Yao Y, Wang Y, Chen L, et al. Clinical utility of PDX cohorts to reveal biomarkers of intrinsic resistance and clonal architecture changes underlying acquired resistance to cetuximab in HNSCC. Signal Transduct Target Ther. 2022; 7(1): 73.

[207]

Kabraji S, Ni J, Sammons S, et al. Preclinical and clinical efficacy of trastuzumab deruxtecan in breast cancer brain metastases. Clin Cancer Res. 2023; 29(1): 174-182.

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