Epithelial–Mesenchymal Transition in Cancer: Insights Into Therapeutic Targets and Clinical Implications

Abstract

Radiation therapy is a fundamental component of cancer treatment, benefiting 50%–70% of patients by selectively targeting malignant tissues. However, radioresistance remains a significant challenge, often driven by epithelial–mesenchymal transition (EMT). EMT increases cancer invasiveness and metastasis by upregulating mesenchymal markers, including vimentin and N-cadherin, and downregulating epithelial markers, such as E-cadherin. EMT under radiation involves principal signaling pathways, including TGF-β, Wnt/β-catenin, Notch, and ERK, which regulate EMT through transcription factors such as Snail, Slug, Twist, and Zeb1/2. These alterations drive cytoskeletal reorganization, decrease cell–cell adhesion, and enhance extracellular matrix degradation via integrins, MMP-2, and MMP-9. We also explored how growth hormones, inflammatory cytokines, and hypoxia in the tumor microenvironment affect radiation-induced EMT. Targeting EMT pathways with monoclonal antibodies and small-molecule inhibitors of signaling pathways may help overcome radioresistance. However, due to the dual role of EMT in cancer progression and tissue regeneration, precise treatment strategies are essential. There is a lack of comprehensive multi-omics studies that provide insights into postradiation EMT progression. This review examines how radiation induces EMT and its impact on metastasis and immune responses while also proposing therapeutic approaches. Integrating EMT-targeting strategies with existing cancer treatments could enhance the effectiveness of radiotherapy and improve patient outcomes.

Keywords

biomarkers / cancer therapy / epithelial–mesenchymal transition / radiation therapy / signaling pathways / tissue injury

References

[1] C. Lachat, P. Peixoto, and E. Hervouet, “Epithelial to Mesenchymal Transition History: From Embryonic Development to Cancers,” Biomolecules 11, no. 6 (2021): 782.

[2] S. Meier and E. D. Hay, “Control of Corneal Differentiation by Extracellular Materials. Collagen as a Promoter and Stabilizer of Epithelial Stroma Production,” Developmental Biology 38, no. 2 (1974): 249-270.

[3] S. Ishikawa, H. Kaneko, T. Sumida, and M. Sekiya, “Ultrastructure of Mesodermal Mixed Tumor of the Uterus,” Acta Patholigica Japonica 29, no. 5 (1979): 801-809.

[4] G. Greenburg and E. D. Hay, “Epithelia Suspended in Collagen Gels Can Lose Polarity and Express Characteristics of Migrating Mesenchymal Cells,” Journal of Cell Biology 95, no. 1 (1982): 333-339.

[5] R. Dulbecco, M. Henahan, M. Bowman, S. Okada, H. Battifora, and M. Unger, “Generation of Fibroblast-Like Cells From Cloned Epithelial Mammary Cells In Vitro: A Possible New Cell Type,” Proceedings of the National Academy of Sciences of the United States of America 78, no. 4 (1981): 2345-2349.

[6] G. Greenburg and E. Hay, “Cytodifferentiation and Tissue Phenotype Change During Transformation of Embryonic Lens Epithelium to Mesenchyme-Like Cells In Vitro,” Developmental Biology 115, no. 2 (1986): 363-379.

[7] M. E. Bilozur and E. D. Hay, “Neural Crest Migration in 3D Extracellular Matrix Utilizes Laminin, Fibronectin, or Collagen,” Developmental Biology 125, no. 1 (1988): 19-33.

[8] E. D. Hay, “Role of Cell-Matrix Contacts in Cell Migration and Epithelial-Mesenchymal Transformation,” Cell Differentiation and Development 32, no. 3 (1990): 367-375.

[9] G. D. Marconi, L. Fonticoli, T. S. Rajan, et al., “Epithelial-Mesenchymal Transition (EMT): The Type-2 EMT in Wound Healing, Tissue Regeneration and Organ Fibrosis,” Cells 10, no. 7 (2021): 1587.

[10] K.-T. Chuang, S.-S. Chiou, and S.-H. Hsu, “Recent Advances in Transcription Factors Biomarkers and Targeted Therapies Focusing on Epithelial-Mesenchymal Transition,” Cancers 15, no. 13 (2023): 3338.

[11] Y.-C. Zhou, J.-Y. Liu, J. Li, et al., “Ionizing Radiation Promotes Migration and Invasion of Cancer Cells Through Transforming Growth Factor-Beta-Mediated Epithelial-Mesenchymal Transition,” International Journal of Radiation Oncology* Biology* Physics 81, no. 5 (2011): 1530-1537.

[12] A. Espinosa-Sánchez, E. Suárez-Martínez, L. Sánchez-Díaz, and A. Carnero, “Therapeutic Targeting of Signaling Pathways Related to Cancer Stemness,” Frontiers in Oncology 10 (2020): 1533.

[13] S. Brabletz, H. Schuhwerk, T. Brabletz, and M. P. Stemmler, “Dynamic EMT: A Multi-Tool for Tumor Progression,” EMBO Journal 40, no. 18 (2021): e108647.

[14] Y. Shang, X. Cai, and D. Fan, “Roles of Epithelial-Mesenchymal Transition in Cancer Drug Resistance,” Current Cancer Drug Targets 13, no. 9 (2013): 915-929.

[15] I. Kazmi, K. S. Alharbi, F. A. Al-Abbasi, et al., “Role of Epithelial-to-Mesenchymal Transition Markers in Different Stages of Endometriosis: Expression of the Snail, Slug, zeb1, and Twist Genes,” Critical Reviews in Eukaryotic Gene Expression 31, no. 2 (2021): 89-95.

[16] E. Bazellières, V. Aksenova, M. Barthélémy-Requin, D. Massey-Harroche, and A. Le Bivic, “Role of the Crumbs Proteins in Ciliogenesis, Cell Migration and Actin Organization,” Seminars in Cell & Developmental Biology 81 (2018): 13-20.

[17] C.-Y. Loh, J. Y. Chai, T. F. Tang, et al., “The E-Cadherin and N-Cadherin Switch in Epithelial-to-Mesenchymal Transition: Signaling, Therapeutic Implications, and Challenges,” Cells 8, no. 10 (2019): 1118.

[18] C. Dos Remedios, D. Chhabra, and M. Kekic, “Actin Binding Proteins: Regulation of Cytoskeletal Microfilaments,” Physiological Reviews 83, no. 2 (2003): 433-473.

[19] S. Edlund, M. Landstrom, C.-H. Heldin, and P. Aspenstrom, “Transforming Growth Factor-β-Induced Mobilization of Actin Cytoskeleton Requires Signaling by Small GTPases Cdc42 and RhoA,” Molecular Biology of the Cell 13, no. 3 (2002): 902-914.

[20] C. T. Mierke, “Mechanical Cues Affect Migration and Invasion of Cells From Three Different Directions,” Frontiers in Cell and Developmental Biology 8 (2020): 583226.

[21] N. Oršolić and M. Jazvinšćak Jembrek, “Molecular and Cellular Mechanisms of Propolis and Its Polyphenolic Compounds Against Cancer,” International Journal of Molecular Sciences 23, no. 18 (2022): 10479.

[22] T. Donnem, A. R. Reynolds, E. A. Kuczynski, et al., “Non-Angiogenic Tumours and Their Influence on Cancer Biology,” Nature Reviews Cancer 18, no. 5 (2018): 323-336.

[23] R. Routledge, “The Surgical Problem of Local Post-Irradiation Effects,” British Journal of Plastic Surgery 7 (1954): 134-152.

[24] J. Locke, S. Karimpour, G. Young, M. A. Lockett, and C. A. Perez, “Radiotherapy for Epithelial Skin Cancer,” International Journal of Radiation Oncology* Biology* Physics 51, no. 3 (2001): 748-755.

[25] X.-C. Liu and P.-K. Zhou, “Tissue Reactions and Mechanism in Cardiovascular Diseases Induced by Radiation,” International Journal of Molecular Sciences 23, no. 23 (2022): 14786.

[26] S. Zhou, M. Zhang, C. Zhou, W. Wang, H. Yang, and W. Ye, “The Role of Epithelial-Mesenchymal Transition in Regulating Radioresistance,” Critical Reviews in Oncology/Hematology 150 (2020): 102961.

[27] D. Srinivasan, R. Subbarayan, M. Krishnan, et al., “Radiation Therapy-Induced Normal Tissue Damage: Involvement of EMT Pathways and Role of FLASH-RT in Reducing Toxicities,” Radiation and Environmental Biophysics 64, no. 1 (2025): 1-16.

[28] J. Kang, E. Kim, W. Kim, et al., “Rhamnetin and Cirsiliol Induce Radiosensitization and Inhibition of Epithelial-Mesenchymal Transition (EMT) by miR-34a-Mediated Suppression of Notch-1 Expression in Non-Small Cell Lung Cancer Cell Lines,” Journal of Biological Chemistry 288, no. 38 (2013): 27343-27357.

[29] E. Al Ageeli, “Dual Roles of MicroRNA-122 in Hepatocellular Carcinoma and Breast Cancer Progression and Metastasis: A Comprehensive Review,” Current Issues in Molecular Biology 46, no. 11 (2024): 11975-11992.

[30] Z. Wang, H. Zhou, F. Cheng, Z. Zhang, and S. Long, “miR-21 Regulates Epithelial-Mesenchymal Transition in Intestinal Fibrosis of Crohn's Disease by Targeting PTEN/mTOR,” Digestive and Liver Disease 54, no. 10 (2022): 1358-1366.

[31] R. Gan, Y. Yang, X. Yang, L. Zhao, J. Lu, and Q. Meng, “Downregulation of miR-221/222 Enhances Sensitivity of Breast Cancer Cells to Tamoxifen Through Upregulation of TIMP3,” Cancer Gene Therapy 21, no. 7 (2014): 290-296.

[32] M. Wang, Z. Huo, X. He, et al., “The Role of miR-29 in the Mechanism of Fibrosis,” Mini Reviews in Medicinal Chemistry 23, no. 19 (2023): 1846-1858.

[33] Y. Tang, Y. Tang, and Y.-S Cheng, “miR-34a Inhibits Pancreatic Cancer Progression Through Snail1-Mediated Epithelial-Mesenchymal Transition and the Notch Signaling Pathway,” Scientific Reports 7, no. 1 (2017): 38232.

[34] Z. Liao, R. Zheng, and G. Shao, “Mechanisms and Application Strategies of miRNA-146a Regulating Inflammation and Fibrosis at Molecular and Cellular Levels,” International Journal of Molecular Medicine 51, no. 1 (2022): 7.

[35] R. Kumarswamy, I. Volkmann, V. Jazbutyte, S. Dangwal, D.-H. Park, and T. Thum, “Transforming Growth Factor-β-Induced Endothelial-to-Mesenchymal Transition Is Partly Mediated by MicroRNA-21,” Arteriosclerosis, Thrombosis, and Vascular Biology 32, no. 2 (2012): 361-369.

[36] C. Yang, S.-D. Zheng, H.-J. Wu, and S.-J. Chen, “Regulatory Mechanisms of the Molecular Pathways in Fibrosis Induced by MicroRNAs,” Chinese Medical Journal 129, no. 19 (2016): 2365-2372.

[37] N. Li, H. Zhou, and Q. Tang, “miR-133: A Suppressor of Cardiac Remodeling?,” Frontiers in Pharmacology 9 (2018): 903.

[38] M. C. Volpe. “miR-200c Prevents and Reverts Lung Fibrosis by Down Regulating Flt1 and Promoting Lung Regeneration” (master's thesis, University of Trieste, 2022), https://arts.units.it/handle/11368/3014982.

[39] B. Cai, L. Yang, Y. Do Jung, et al., “PTEN: An Emerging Potential Target for Therapeutic Intervention in Respiratory Diseases,” Oxidative Medicine and Cellular Longevity 2022, no. 1 (2022): 4512503.

[40] H. Wang, K. Sun, H. Peng, Y. Wang, and L. Zhang, “Emerging Roles of Noncoding RNAs in Idiopathic Pulmonary Fibrosis,” Cell Death Discovery 10, no. 1 (2024): 443.

[41] L. Cushing, P. Kuang, and J. Lü, “The Role of miR-29 in Pulmonary Fibrosis,” Biochemistry and Cell Biology 93, no. 2 (2015): 109-118.

[42] J. Guo, M. Liao, and J. Wang, “TLR4 signaling in the Development of Colitis-Associated Cancer and Its Possible Interplay With MicroRNA-155,” Cell Communication and Signaling 19 (2021): 90.

[43] S. Noguchi and A. Matsui, “MicroRNA-203 Inhibits Migration and Invasion of Canine Tonsillar Squamous Cell Carcinoma Cells by Targeting SLUG,” Frontiers in Veterinary Science 10 (2023): 1239224.

[44] P.-Y. Chu, F.-W. Hu, C.-C. Yu, et al., “Epithelial-Mesenchymal Transition Transcription Factor ZEB1/ZEB2 Co-Expression Predicts Poor Prognosis and Maintains Tumor-Initiating Properties in Head and Neck Cancer,” Oral Oncology 49, no. 1 (2013): 34-41.

[45] P. A. Ajuyah. “The Role of miR-21 and miR-499 in Head and Neck cancer” (PhD diss., University of Technology Sydney, 2016). https://opus.lib.uts.edu.au/bitstream/10453/90016/2/02whole.pdf.

[46] B. Bhattacharjee, A. F. Syeda, D. Rynjah, et al., “Pharmacological Impact of MicroRNAs in Head and Neck Squamous Cell Carcinoma: Prevailing Insights on Molecular Pathways, Diagnosis, and Nanomedicine Treatment,” Frontiers in Pharmacology 14 (2023): 1174330.

[47] Z. Sun, W. Hu, J. Xu, A. M. Kaufmann, and A. E. Albers, “MicroRNA-34a Regulates Epithelial-Mesenchymal Transition and Cancer Stem Cell Phenotype of Head and Neck Squamous Cell Carcinoma In Vitro,” International Journal of Oncology 47, no. 4 (2015): 1339-1350.

[48] A. C.-K. Chung and H. Y. Lan, “MicroRNAs in Renal Fibrosis,” Frontiers in Physiology 6 (2015): 50.

[49] J. Guo, “Effect of miR-21 on Renal Fibrosis Induced by Nano-SiO₂ in Diabetic Nephropathy Rats via PTEN/AKT Pathway,” Journal of Nanoscience and Nanotechnology 21, no. 2 (2021): 1079-1084.

[50] M. Xiong, L. Jiang, Y. Zhou, et al., “The miR-200 Family Regulates TGF-β1-Induced Renal Tubular Epithelial to Mesenchymal Transition Through Smad Pathway by Targeting ZEB1 and ZEB2 Expression,” American Journal of Physiology-Renal Physiology 302, no. 3 (2012): F369-F379.

[51] J. Li, X. Yan, Z. Wu, et al., “Role of miRNAs in Macrophage-Mediated Kidney Injury,” Pediatric Nephrology 39 (2024): 3397-3410.

[52] A. S. Doghish, A. A. El-Husseiny, N. M. Abdelmaksoud, et al., “The Interplay of Signaling Pathways and miRNAs in the Pathogenesis and Targeted Therapy of Esophageal Cancer,” Pathology-Research and Practice 246 (2023): 154529.

[53] S. Sinha, L. D. Boila, S. S. Chatterjee, and A. Sengupta, “miRNA and Cancer: A Deadly Liaison?,” in Cancer and Noncoding RNAs, ed. J. Chakrabarti and S. Mitra (Academic Press, 2018), 27-46.

[54] S. P. Papadakos, A. Argyrou, V. Lekakis, et al., “Metformin in Esophageal Carcinoma: Exploring Molecular Mechanisms and Therapeutic Insights,” International Journal of Molecular Sciences 25, no. 5 (2024): 2978.

[55] X. Zhou, Y. Wang, B. Shan, et al., “The Downregulation of miR-200c/141 Promotes ZEB1/2 Expression and Gastric Cancer Progression,” Medical Oncology 32 (2015): 428.

[56] M. Zheng, Y.-P Jiang, W. Chen, et al., “Snail and Slug Collaborate on EMT and Tumor Metastasis Through miR-101-Mediated EZH2 Axis in Oral Tongue Squamous Cell Carcinoma,” Oncotarget 6, no. 9 (2015): 6794.

[57] N. Cong, P. Du, A. Zhang, et al., “Downregulated MicroRNA-200a Promotes EMT and Tumor Growth Through the Wnt/β-Catenin Pathway by Targeting the E-Cadherin Repressors ZEB1/ZEB2 in Gastric Adenocarcinoma,” Oncology Reports 29, no. 4 (2013): 1579-1587.

[58] S. Najjary, R. Mohammadzadeh, A. Mokhtarzadeh, A. Mohammadi, A. B. Kojabad, and B. KojabadBaradaran, “Role of miR-21 as an Authentic Oncogene in Mediating Drug Resistance in Breast Cancer,” Gene 738 (2020): 144453.

[59] S.-J. He, C.-Q. Xiang, Y. Zhang, X.-T. Lu, H.-W. Chen, and L.-X. Xiong, “Recent Progress on the Effects of MicroRNAs and Natural Products on Tumor Epithelial-Mesenchymal Transition,” OncoTargets and Therapy 10 (2017): 3435-3451.

[60] T. Sirek, A. Sirek, P. Borawski, et al., “miRNAs in Signal Transduction of SMAD Proteins in Breast Cancer,” International Journal of Molecular Sciences 25, no. 18 (2024): 10088.

[61] G. Wang, J. J. Wang, H. M. Tang, and S. S. T. To, “Targeting Strategies on miRNA-21 and PDCD4 for Glioblastoma,” Archives of Biochemistry and Biophysics 580 (2015): 64-74.

[62] L. Li and H. Li, “Role of MicroRNA-Mediated MMP Regulation in the Treatment and Diagnosis of Malignant Tumors,” Cancer Biology & Therapy 14, no. 9 (2013): 796-805.

[63] Y. Song, J. Li, Y. Zhu, et al., “MicroRNA-9 Promotes Tumor Metastasis via Repressing E-Cadherin in Esophageal Squamous Cell Carcinoma,” Oncotarget 5, no. 22 (2014): 11669.

[64] L. Soleymani, A. Zarrabi, F. Hashemi, et al., “Role of ZEB Family Members in Proliferation, Metastasis, and Chemoresistance of Prostate Cancer Cells: Revealing Signaling Networks,” Current Cancer Drug Targets 21, no. 9 (2021): 749-767.

[65] Y.-J. Choi, G.-Y. Baek, H.-R. Park, S.-K. Jo, and U. Jung, “Smad2/3-Regulated Expression of DLX2 Is Associated With Radiation-Induced Epithelial-Mesenchymal Transition and Radioresistance of A549 and MDA-MB-231 Human Cancer Cell Lines,” PLoS ONE 11, no. 1 (2016): e0147343.

[66] A. Vidal and T. Redmer, “Decoding the Role of CD271 in Melanoma,” Cancers 12, no. 9 (2020): 2460.

[67] J. Wang, M. Kang, Q. Wen, et al., “Berberine Sensitizes Nasopharyngeal Carcinoma Cells to Radiation Through Inhibition of Sp1 and EMT,” Oncology Reports 37, no. 4 (2017): 2425-2432.

[68] B. Zou, X.-L. Zhou, S.-Q. Lai, and J.-C. Liu, “Notch Signaling and Non-Small Cell Lung Cancer,” Oncology Letters 15, no. 3 (2018): 3415-3421.

[69] S. S. Nagaraja and D. Nagarajan, “Radiation-Induced Pulmonary Epithelial-Mesenchymal Transition: A Review on Targeting Molecular Pathways and Mediators,” Current Drug Targets 19, no. 10 (2018): 1191-1204.

[70] J. Kozak, A. Forma, M. Czeczelewski, et al., “Inhibition or Reversal of the Epithelial-Mesenchymal Transition in Gastric Cancer: Pharmacological Approaches,” International Journal of Molecular Sciences 22, no. 1 (2020): 277.

[71] M. Bai, X. Ma, X. Li, et al., “The Accomplices of NF-κB Lead to Radioresistance,” Current Protein and Peptide Science 16, no. 4 (2015): 279-294.

[72] L. Qiao, Y. Chen, N. Liang, et al., “Targeting Epithelial-to-Mesenchymal Transition in Radioresistance: Crosslinked Mechanisms and Strategies,” Frontiers in Oncology 12 (2022): 775238.

[73] M. J. Tahmasebi-Birgani, A. Teimoori, A. Ghadiri, H. Mansoury-Asl, A. Danyaei, and H. Khanbabaei, “Fractionated Radiotherapy Might Induce Epithelial-Mesenchymal Transition and Radioresistance in a Cellular Context Manner,” Journal of Cellular Biochemistry 120, no. 5 (2019): 8601-8610.

[74] U. Sharma, M. Murmu, T. S. Barwal, et al., “A Pleiotropic Role of Long Non-Coding RNAs in the Modulation of Wnt/β-Catenin and PI3K/Akt/mTOR Signaling Pathways in Esophageal Squamous Cell Carcinoma: Implication in Chemotherapeutic Drug Response,” Current Oncology 29, no. 4 (2022): 2326-2349.

[75] LGdR Bastos, P. G. de Marcondes, J. C. M. de-Freitas-Junior, et al., “Progeny From Irradiated Colorectal Cancer Cells Acquire an EMT-Like Phenotype and Activate Wnt/β-Catenin Pathway,” Journal of Cellular Biochemistry 115, no. 12 (2014): 2175-2187.

[76] M. Cojoc, C. Peitzsch, I. Kurth, et al., “Aldehyde Dehydrogenase Is Regulated by β-Catenin/TCF and Promotes Radioresistance in Prostate Cancer Progenitor Cells,” Cancer Research 75, no. 7 (2015): 1482-1494.

[77] Y. Zhao, J. Yi, L. Tao, et al., “Wnt Signaling Induces Radioresistance Through Upregulating HMGB1 in Esophageal Squamous Cell Carcinoma,” Cell Death & Disease 9, no. 4 (2018): 433.

[78] P.-B. Han, X.-J. Ji, M. Zhang, and L.-Y. Gao, “Upregulation of lncRNA LINC00473 Promotes Radioresistance of HNSCC Cells Through Activating Wnt/β-Catenin Signaling Pathway,” European Review for Medical & Pharmacological Sciences 22, no. 21 (2018): 7305-7313.

[79] A. A. Adjei and M. Hidalgo, “Intracellular Signal Transduction Pathway Proteins as Targets for Cancer Therapy,” Journal of Clinical Oncology 23, no. 23 (2005): 5386-5403.

[80] A. L. Hein, M. M. Ouellette, and Y. Yan, “Radiation-Induced Signaling Pathways That Promote Cancer Cell Survival,” International Journal of Oncology 45, no. 5 (2014): 1813-1819.

[81] C. Galeaz, C. Totis, and A. Bisio, “Radiation Resistance: A Matter of Transcription Factors,” Frontiers in Oncology 11 (2021): 662840.

[82] A. Stulpinas, M. Sereika, A. Vitkeviciene, A. Imbrasaite, N. Krestnikova, and A. V. Kalvelyte, “Crosstalk Between Protein Kinases AKT and ERK1/2 in Human Lung Tumor-Derived Cell Models,” Frontiers in Oncology 12 (2023): 1045521.

[83] A. Cevenini, S. Orrù, A. Mancini, A. Alfieri, P. Buono, and E. Imperlini, “Molecular Signatures of the Insulin-Like Growth Factor 1-Mediated Epithelial-Mesenchymal Transition in Breast, Lung and Gastric Cancers,” International Journal of Molecular Sciences 19, no. 8 (2018): 2411.

[84] Y. Cheng, J. Chen, Y. Shi, X. Fang, and Z. Tang, “MAPK Signaling Pathway in Oral Squamous Cell Carcinoma: Biological Function and Targeted Therapy,” Cancers 14, no. 19 (2022): 4625.

[85] L. Zhang, W. Chen, S. Liu, and C. Chen, “Targeting Breast Cancer Stem Cells,” International Journal of Biological Sciences 19, no. 2 (2023): 552.

[86] S. Aashaq, A. Batool, S. A. Mir, M. A. Beigh, K. I. Andrabi, and Z. A. Shah, “TGF-β Signaling: A Recap of SMAD-Independent and SMAD-Dependent Pathways,” Journal of Cellular Physiology 237, no. 1 (2022): 59-85.

[87] G. Khalili-Tanha, E. S. Radisky, D. C. Radisky, and A. Shoari, “Matrix Metalloproteinase-Driven Epithelial-Mesenchymal Transition: Implications in Health and Disease,” Journal of Translational Medicine 23, no. 1 (2025): 436.

[88] L. Meng, S. Liu, J. Luo, et al., “Oxidative Stress and Reactive Oxygen Species in Otorhinolaryngological Diseases: Insights From Pathophysiology to Targeted Antioxidant Therapies,” Redox Report 30, no. 1 (2025): 2458942.

[89] M. Fasano, M. Pirozzi, C. C. Miceli, et al., “TGF-β Modulated Pathways in Colorectal Cancer: New Potential Therapeutic Opportunities,” International Journal of Molecular Sciences 25, no. 13 (2024): 7400.

[90] T. Shibue, and R. A. Weinberg, “EMT, CSCs, and Drug Resistance: The Mechanistic Link and Clinical Implications,” Nature Reviews Clinical Oncology 14, no. 10 (2017): 611-629.

[91] A. Dave, F. Parande, E.-J. Park, and J. M. Pezzuto, “Phytochemicals and Cancer Chemoprevention,” Journal of Cancer Metastasis and Treatment 6 (2020): 46.

[92] M. A. Kamal, Y. M. Mandour, M. K. Abd El-Aziz, U. Stein, and H. M. El Tayebi, “Small Molecule Inhibitors for Hepatocellular Carcinoma: Advances and Challenges,” Molecules 27, no. 17 (2022): 5537.

[93] M. Negrette-Guzman, “Combinations of the Antioxidants Sulforaphane or Curcumin and the Conventional Antineoplastics Cisplatin or Doxorubicin as Prospects for Anticancer Chemotherapy,” European Journal of Pharmacology 859 (2019): 172513.

[94] J. Gupta, A. T. Ahmed, N. A. Tayyib, et al., “A State-of-Art of Underlying Molecular Mechanisms and Pharmacological Interventions/Nanotherapeutics for Cisplatin Resistance in Gastric Cancer,” Biomedicine & Pharmacotherapy 166 (2023): 115337.

[95] H. Romano, K. Lin, S. Vivarelli, L. Falzone, M. Libra, and B. Bonavida, “Resistance of HER2-Expressing Breast Cancer Patients Treated With Trastuzumab: Underlying Mechanisms of Resistance and Reversals,” in Overcoming Cancers Resistant to HER-2 Antibodies, ed. B. Bonavida (Academic Press, 2024), 19-43.

[96] D. W. Edwardson, A. M. Parissenti, and A. T. Kovala, “Chemotherapy and Inflammatory Cytokine Signalling in Cancer Cells and the Tumour Microenvironment,” in Breast Cancer Metastasis and Drug Resistance: Challenges and Progress ed. A. Ahmad (Springer, 2019), 173-215.

[97] R. Farghadani and R. Naidu, “Curcumin as an Enhancer of Therapeutic Efficiency of Chemotherapy Drugs in Breast Cancer,” International Journal of Molecular Sciences 23, no. 4 (2022): 2144.

[98] W. S. Tong, “New Drug Combinations to Overcome Resistance to EGFR Targeted Therapy or Chemotherapy in Lung Cancer” (PhD diss., The Chinese University of Hong Kong, 2020), https://www.proquest.com/openview/1b81a724dcd7eb6b633bf229a325edea/1?pq-origsite=gscholar&cbl=2026366&diss=y.

[99] J. D. Monroe, S. A. Moolani, E. N. Irihamye, et al., “Cisplatin and Phenanthriplatin Modulate Long-Noncoding RNA Expression in A549 and IMR90 Cells Revealing Regulation of MicroRNAs, Wnt/β-Catenin and TGF-β Signaling,” Scientific Reports 11, no. 1 (2021): 10408.

[100] M. Yang, M. Cui, Y. Sun, S. Liu, and W. Jiang, “Mechanisms, Combination Therapy, and Biomarkers in Cancer Immunotherapy Resistance,” Cell Communication and Signaling 22, no. 1 (2024): 338.

[101] A. Guidi, C. Codecà, and D. Ferrari, “Chemotherapy and Immunotherapy for Recurrent and Metastatic Head and Neck Cancer: A Systematic Review,” Medical Oncology 35, no. 3 (2018): 37.

[102] K. F. Alchin. “Ototoxicity in Patients Receiving Concurrent Cisplatin and Cranial Irradiation Therapy for the Treatment of Head and Neck Cancers: An Audiometric Follow-Up” (master's thesis, University of Canterbury, 2010), https://ir.canterbury.ac.nz/server/api/core/bitstreams/f04b6e59-cd52-48dd-ab90-44a0346d42e9/content.

[103] Z.-X. Yuan, J. Mo, G. Zhao, G. Shu, H-l Fu, and W. Zhao, “Targeting Strategies for Renal Cell Carcinoma: From Renal Cancer Cells to Renal Cancer Stem Cells,” Frontiers in Pharmacology 7 (2016): 423.

[104] Q.-X. Teng, Y. V. Ashar, P. Gupta, et al., “Revisiting mTOR Inhibitors as Anticancer Agents,” Drug Discovery Today 24, no. 10 (2019): 2086-2095.

[105] C. Yang, Z. Mai, C. Liu, S. Yin, Y. Cai, and C. Xia, “Natural Products in Preventing Tumor Drug Resistance and Related Signaling Pathways,” Molecules 27, no. 11 (2022): 3513.

[106] P. B. Tchounwou, S. Dasari, F. K. Noubissi, P. Ray, and S. Kumar, “Advances in Our Understanding of the Molecular Mechanisms of Action of Cisplatin in Cancer Therapy,” Journal of Experimental Pharmacology 13 (2021): 303-328.

[107] M. Vellengara, “A Comparative Study of Treatment Response and Toxicities in Concurrent Chemoradiation With Cisplatin Alone Versus Cisplatin and Paclitaxel in Locally Advanced Esophageal Carcinoma” (PhD diss., Rajiv Gandhi University of Health Sciences, 2017), https://www.proquest.com/openview/00bc26ed890f2172bf244f7c4f94326b/1?pq-origsite=gscholar&cbl=2026366&diss=y.

[108] F. Cucchiara, S. Ferraro, G. Luci, and G. Bocci, “Relevant Pharmacological Interactions Between Alkylating Agents and Antiepileptic Drugs: Preclinical and Clinical Data,” Pharmacological Research 175 (2022): 105976.

[109] S. Riondino, G. Del Monte, F. Fratangeli, F. Guadagni, M. Roselli, and P. Ferroni, “Anti-Angiogenic Drugs, Vascular Toxicity and Thromboembolism in Solid Cancer,” Cardiovascular & Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Cardiovascular & Hematological Agents) 15, no. 1 (2017): 3-16.

[110] Y. Li, “DNA Adducts in Cancer Chemotherapy,” Journal of Medicinal Chemistry 67, no. 7 (2024): 5113-5143.

[111] R. Thapa, O. Afzal, G. Gupta, et al., “Unveiling the Connection: Long-Chain Non-Coding RNAs and Critical Signaling Pathways in Breast Cancer,” Pathology-Research and Practice 249 (2023): 154736.

[112] L. B. Darragh, A. J. Oweida, and S. D. Karam, “Overcoming Resistance to Combination Radiation-Immunotherapy: A Focus on Contributing Pathways Within the Tumor Microenvironment,” Frontiers in Immunology 9 (2019): 3154.

[113] E. Nevedomskaya and B. Haendler, “From Omics to Multi-Omics Approaches for in-Depth Analysis of the Molecular Mechanisms of Prostate Cancer,” International Journal of Molecular Sciences 23, no. 11 (2022): 6281.

[114] H. Pei, W. Guo, Y. Peng, H. Xiong, and Y. Chen, “Targeting Key Proteins Involved in Transcriptional Regulation for Cancer Therapy: Current Strategies and Future Prospective,” Medicinal Research Reviews 42, no. 4 (2022): 1607-1660.

[115] Z. U. Din, B. Cui, C. Wang, et al., “Crosstalk Between Lipid Metabolism and EMT: Emerging Mechanisms and Cancer Therapy,” Molecular and Cellular Biochemistry 480 (2024): 103-118.

[116] Q. Wang, B. Šabanović, A. Awada, et al., “Single-Cell Omics: A New Perspective for Early Detection of Pancreatic Cancer?,” European Journal of Cancer 190 (2023): 112940.

[117] A. Orsini, C. Diquigiovanni, and E. Bonora, “Omics Technologies Improving Breast Cancer Research and Diagnostics,” International Journal of Molecular Sciences 24, no. 16 (2023): 12690.

[118] E. Nowak and I. Bednarek, “Aspects of the Epigenetic Regulation of EMT Related to Cancer Metastasis,” Cells 10, no. 12 (2021): 3435.

[119] I. V. Bure, M. V. Nemtsova, and D. V. Zaletaev, “Roles of E-Cadherin and Noncoding RNAs in the Epithelial-Mesenchymal Transition and Progression in Gastric Cancer,” International Journal of Molecular Sciences 20, no. 12 (2019): 2870.

[120] F. Maroufi, A. Maali, M. Abdollahpour-Alitappeh, M. H. Ahmadi, and M. Azad, “CRISPR-Mediated Modification of DNA Methylation Pattern in the New Era of Cancer Therapy,” Epigenomics 12, no. 20 (2020): 1845-1859.

[121] R. Mohammadinejad, A. Biagioni, G. Arunkumar, et al., “EMT Signaling: Potential Contribution of CRISPR/Cas Gene Editing,” Cellular and Molecular Life Sciences 77 (2020): 2701-2722.

[122] S. Mehrabadi, F. S. Izadi, S. Pasha, et al., “The Potential Therapeutic Applications of CRISPR/Cas9 in the Treatment of Gastrointestinal Cancers,” Current Molecular Medicine 25 (2024): 278-288.

[123] S. S. Messeha, N. O. Zarmouh, and K. F. Soliman, “Polyphenols Modulating Effects of PD-L1/PD-1 Checkpoint and EMT-Mediated PD-L1 Overexpression in Breast Cancer,” Nutrients 13, no. 5 (2021): 1718.

[124] S. Romano, M. Tufano, P. D'Arrigo, V. Vigorito, S. Russo, and M. F. Romano, “Cell Stemness, Epithelial-to-Mesenchymal Transition, and Immunoevasion: Intertwined Aspects in Cancer Metastasis” Seminars in Cancer Biology 60 (2020): 181-190.

[125] Y. Jiang and H. Zhan, “Communication Between EMT and PD-L1 Signaling: New Insights Into Tumor Immune Evasion,” Cancer Letters 468 (2020): 72-81.

[126] A. Rayford, F. Gärtner, M. P. Ramnefjell, et al., “AXL Expression Reflects Tumor-Immune Cell Dynamics Impacting Outcome in Non-Small Cell Lung Cancer Patients Treated With Immune Checkpoint Inhibitor Monotherapy,” Frontiers in Immunology 15 (2024): 1444007.

[127] Q. Peña, A. Wang, O. Zaremba, et al., “Metallodrugs in Cancer Nanomedicine,” Chemical Society Reviews 51, no. 7 (2022): 2544-2582.

[128] A. Libra, E. Sciacca, G. Muscato, G. Sambataro, L. Spicuzza, and C. Vancheri, “Highlights on Future Treatments of IPF: Clues and Pitfalls,” International Journal of Molecular Sciences 25, no. 15 (2024): 8392.

[129] H. Su, X. Jin, and X. Zhang, “FH535 Increases the Radiosensitivity and Reverses Epithelial-to-Mesenchymal Transition of Radioresistant Esophageal Cancer Cell Line KYSE-150R,” Journal of Translational Medicine 13 (2015): 104.

[130] X. Yuan, H. Wu, N. Han, et al., “Notch Signaling and EMT in Non-Small Cell Lung Cancer: Biological Significance and Therapeutic Application,” Journal of Hematology & Oncology 7 (2014): 87.

[131] D. Wu, S. Tian, and W. Zhu, “Modulating Multidrug Resistance to Drug-Based Antitumor Therapies Through NF-κB Signaling Pathway: Mechanisms and Perspectives,” Expert Opinion on Therapeutic Targets 27, no. 6 (2023): 503-515.

[132] W. Manni and W. Min, “Signaling Pathways in the Regulation of Cancer Stem Cells and Associated Targeted Therapy,” MedComm 3, no. 4 (2022): e176.

[133] V. Parvathaneni, S. K. Shukla, and V. Gupta, “Emerging Therapeutic Targets and Therapies in Idiopathic Pulmonary Fibrosis,” in Fibrosis in Disease: An Organ-Based Guide to Disease Pathophysiology and Therapeutic Considerations, ed. M. S. Willis, C. C. Yates, and J. C. Schisler (Humana Press, 2019): 197-237.

[134] R. Kulshrestha, P. Kumar, A. Singh, and D. S. Nair, “Regulation of TGF-β1-Smad-1-7 Signaling to Inhibit Epithelial Mesenchymal Transition by Repurposed Anti-Fibrotic Drug Pirfenidone Can Attenuate Lung Cancer Progression,” Journal of Cancer Science and Clinical Therapeutics 7, no. 1 (2023): 50-64.

[135] C. Landi, A. Carleo, L. Vantaggiato, et al., “Common Molecular Pathways Targeted by Nintedanib in Cancer and IPF: A Bioinformatic Study,” Pulmonary Pharmacology & Therapeutics 64 (2020): 101941.

[136] X. Kang, S. Jadhav, M. Annaji, et al., “Advancing Cancer Therapy With Copper/Disulfiram Nanomedicines and Drug Delivery Systems,” Pharmaceutics 15, no. 6 (2023): 1567.

[137] M. J. Saadh, P. Sharma, I. H. Naser, et al., “Epithelial-Mesenchymal Transition in Chemoradiation-Induced Lung Damage: Mechanisms and Potential Treatment Approaches,” Journal of Biochemical and Molecular Toxicology 38, no. 8 (2024): e23790.

[138] Z. Javed, K. Khan, A. Rasheed, et al., “MicroRNAs and Natural Compounds Mediated Regulation of TGF Signaling in Prostate Cancer,” Frontiers in Pharmacology 11 (2021): 613464.

[139] M. Tafrihi and R. Nakhaei Sistani, “E-Cadherin/β-Catenin Complex: A Target for Anticancer and Antimetastasis Plants/Plant-Derived Compounds,” Nutrition and Cancer 69, no. 5 (2017): 702-722.

[140] L. Avila-Carrasco, P. Majano, and J. A. Sánchez-Toméro, et al., “Natural Plants Compounds as Modulators of Epithelial-to-Mesenchymal Transition,” Frontiers in Pharmacology 10 (2019): 715.

[141] H. L. Ang, C. D. Mohan, M. K. Shanmugam, et al., “Mechanism of Epithelial-Mesenchymal Transition in Cancer and Its Regulation by Natural Compounds,” Medicinal Research Reviews 43, no. 4 (2023): 1141-1200.

[142] Z. Xu, Y. Zhang, H. Dai, and B. Han, “Epithelial-Mesenchymal Transition-Mediated Tumor Therapeutic Resistance,” Molecules 27, no. 15 (2022): 4750.

[143] M. Honari, R. Shafabakhsh, R. J. Reiter, H. Mirzaei, and Z. Asemi, “Resveratrol Is a Promising Agent for Colorectal Cancer Prevention and Treatment: Focus on Molecular Mechanisms,” Cancer Cell International 19 (2019): 180.

[144] A. Lyakhovich and M. E. Lleonart, “Bypassing Mechanisms of Mitochondria-Mediated Cancer Stem Cells Resistance to Chemo-and Radiotherapy,” Oxidative Medicine and Cellular Longevity 2016, no. 1 (2016): 1716341.

[145] H. Liang, Z. Chen, R. Yang, et al., “Methyl Gallate Suppresses the Migration, Invasion, and Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma Cells via the AMPK/NF-κB Signaling Pathway In Vitro and In Vivo,” Frontiers in Pharmacology 13 (2022): 894285.

[146] P. Gawali, A. Saraswat, S. Bhide, S. Gupta, and K. Patel, “Human Solid Tumors and Clinical Relevance of the Enhanced Permeation and Retention Effect: A ‘Golden Gate’ for Nanomedicine in Preclinical Studies?,” Nanomedicine 18, no. 2 (2023): 169-190.

[147] M. Tangsiri, A. Hheidari, M. Liaghat, et al., “Promising Applications of Nanotechnology in Inhibiting Chemo-Resistance in Solid Tumors by Targeting Epithelial-Mesenchymal Transition (EMT),” Biomedicine & Pharmacotherapy 170 (2024): 115973.

[148] M. Cordani, R. Strippoli, and Á. Somoza, “Nanomaterials as Inhibitors of Epithelial Mesenchymal Transition in Cancer Treatment,” Cancers 12, no. 1 (2019): 25.

[149] S. Naghizadeh, A. Mohammadi, B. Baradaran, and B. Mansoori, “Overcoming Multiple Drug Resistance in Lung Cancer Using siRNA Targeted Therapy,” Gene 714 (2019): 143972.

[150] P. Sen, M. Saha, and S. S. Ghosh, “Nanoparticle Mediated Alteration of EMT Dynamics: An Approach to Modulate Cancer Therapeutics,” Materials Advances 1, no. 8 (2020): 2614-2630.

[151] P. Garg, J. Malhotra, P. Kulkarni, D. Horne, R. Salgia, and S. S. Singhal, “Emerging Therapeutic Strategies to Overcome Drug Resistance in Cancer Cells,” Cancers 16, no. 13 (2024): 2478.

[152] T. Tsao, J. Beretov, J. Ni, et al., “Cancer Stem Cells in Prostate Cancer Radioresistance,” Cancer Letters 465 (2019): 94-104.

[153] M. N. Mills, C. Walker, C. Thawani, et al., “Trastuzumab Emtansine (T-DM1) and Stereotactic Radiation in the Management of HER2⁺ Breast Cancer Brain Metastases,” BMC cancer 21 (2021): 223.

[154] Y.-C. Zhang, Y.-T. Zhang, Y. Wang, Y. Zhao, and L.-J. He, “What Role Does PDL1 Play in EMT Changes in Tumors and Fibrosis?,” Frontiers in Immunology 14 (2023): 1226038.

[155] M. E. Neganova, S. G. Klochkov, Y. R. Aleksandrova, and G. Aliev, “Histone Modifications in Epigenetic Regulation of Cancer: Perspectives and Achieved Progress,” Seminars in Cancer Biology 83 (2022): 452-471.

[156] A. Kim, K. Mo, H. Kwon, et al., “Epigenetic Regulation in Breast Cancer: Insights on Epidrugs,” Epigenomes 7, no. 1 (2023): 6.

[157] A. Majchrzak-Celińska, A. Warych, and M. Szoszkiewicz, “Novel Approaches to Epigenetic Therapies: From Drug Combinations to Epigenetic Editing,” Genes 12, no. 2 (2021): 208.

[158] Y. Wang, Y. Han, Y. Jin, Q. He, and Z. Wang, “The Advances in Epigenetics for Cancer Radiotherapy,” International Journal of Molecular Sciences 23, no. 10 (2022): 5654.

[159] T. Tan, P. Shi, M. N. Abbas, et al., “Epigenetic Modification Regulates Tumor Progression and Metastasis Through EMT,” International Journal of Oncology 60, no. 6 (2022): 70.

[160] Y.-A. Shen, C.-C. Chen, B.-J. Chen, et al., “Potential Therapies Targeting Metabolic Pathways in Cancer Stem Cells,” Cells 10, no. 7 (2021): 1772.

[161] I. Georgakopoulos-Soares, D. V. Chartoumpekis, V. Kyriazopoulou, and A. Zaravinos, “EMT Factors and Metabolic Pathways in Cancer,” Frontiers in Oncology 10 (2020): 499.

[162] T.-W. Kao, Y.-C. Chuang, H.-L. Lee, C.-C. Kuo, and Y.-A. Shen, “Therapeutic Targeting of Glutaminolysis as a Novel Strategy to Combat Cancer Stem Cells,” International Journal of Molecular Sciences 23, no. 23 (2022): 15296.

[163] A. Romo-Perez, G. Domínguez-Gómez, A. D. Chávez-Blanco, A. González-Fierro, J. Correa-Basurto, and A. Dueñas-González, “PaSTe. Blockade of the Lipid Phenotype of Prostate Cancer as Metabolic Therapy: A Theoretical Proposal,” Current Medicinal Chemistry 31, no. 22 (2024): 3265-3285.

[164] E. Amengual-Cladera, P. M. Morla-Barcelo, A. Morán-Costoya, et al., “Metformin: From Diabetes to Cancer—Unveiling Molecular Mechanisms and Therapeutic Strategies,” Biology 13, no. 5 (2024): 302.

[165] M. Zhang, D.-Y. Yang, Z.-Y. He, et al., “Auranofin Inhibits the Occurrence of Colorectal Cancer by Promoting mTOR-Dependent Autophagy and Inhibiting Epithelial-Mesenchymal Transformation,” Anti-Cancer Drugs 35, no. 2 (2024): 129-139.

[166] B. Aschenbrenner, G. Negro, D. Savic, et al., “Simvastatin Is Effective in Killing the Radioresistant Breast Carcinoma Cells,” Radiology and Oncology 55, no. 3 (2021): 305-316.

[167] S. Pal, A. Sharma, S. P. Mathew, and B. G. Jaganathan, “Targeting Cancer-Specific Metabolic Pathways for Developing Novel Cancer Therapeutics,” Frontiers in Immunology 13 (2022): 955476.

[168] L. Singh, L. Nair, D. Kumar, et al., “Hypoxia Induced Lactate Acidosis Modulates Tumor Microenvironment and Lipid Reprogramming to Sustain the Cancer Cell Survival,” Frontiers in Oncology 13 (2023): 1034205.

[169] T. Liu, S. Han, Y. Yao, and G. Zhang, “Role of Human Monocarboxylate Transporter 1 (hMCT1) and 4 (hMCT4) in Tumor Cells and the Tumor Microenvironment,” Cancer Management and Research 15 (2023): 957-975.

[170] K. A. Sheikh, M. Amjad, M. T. Irfan, et al., “Exploring TGF-β Signaling in Cancer Progression: Prospects and Therapeutic Strategies,” OncoTargets and Therapy 18 (2025): 233-262.

[171] J. Park, J. Choi, I. Cho, and Y. Y. Sheen, “Radiotherapy-Induced Oxidative Stress and Fibrosis in Breast Cancer Are Suppressed by Vactosertib, a Novel, Orally Bioavailable TGF-β/ALK5 Inhibitor,” Scientific Reports 12, no. 1 (2022): 16104.

[172] A. K. Borah, C. S. Singh, B. Kharbuli, A. Chatterjee, S. Chakrabarty, and A. Das, “The Emerging Role of the γ-Secretase Inhibitors in Cancer Management,” in Handbook of Proteases in Cancer, ed. S. Chakraborti (CRC Press, 2024), 162-178.

[173] Y. Chen, M. Chen, and K. Deng, “Blocking the Wnt/β-Catenin Signaling Pathway to Treat Colorectal Cancer: Strategies to Improve Current Therapies,” International Journal of Oncology 62, no. 2 (2022): 24.

[174] M. H. Barcellos-Hoff, J. L. Gulley, “Molecular Pathways and Mechanisms of TGFβ in Cancer Therapy,” Clinical Cancer Research 29, no. 11 (2023): 2025-2033.

[175] H. Y. Lim, J. Heo, J. A. Peguero, et al., “Efficacy and Safety of Bintrafusp Alfa in 2 Phase I Expansion Cohorts With Advanced HCC,” Hepatology 81, no. 1 (2025): 32-43.

[176] D. Srinivasan, R. Subbarayan, N. Srivastava, et al., “A Comprehensive Overview of Radiation Therapy Impacts of Various Cancer Treatments and Pivotal Role in the Immune System,” Cell Biochemistry and Function 42, no. 6 (2024): e4103.

[177] Y. Xie, P. Li, Y. Gao, et al., “Reduced E-Cadherin Expression Is Correlated With Poor Prognosis in Patients With Bladder Cancer: A Systematic Review and Meta-Analysis,” Oncotarget 8, no. 37 (2017): 62489.

[178] Y. Chen, Y. Ji, L. Shen, et al., “High Core 1β1, 3-Galactosyltransferase 1 Expression Is Associated With Poor Prognosis and Promotes Cellular Radioresistance in Lung Adenocarcinoma,” Journal of Cancer Research and Clinical Oncology 150, no. 4 (2024): 214.

[179] M. Garg, “Emerging Roles of Epithelial-Mesenchymal Plasticity in Invasion-Metastasis Cascade and Therapy Resistance,” Cancer and Metastasis Reviews 41, no. 1 (2022): 131-145.

[180] L. Ding, H. Gu, X. Xiong, et al., “MicroRNAs Involved in Carcinogenesis, Prognosis, Therapeutic Resistance, and Applications in Human Triple-Negative Breast Cancer,” Cells 8, no. 12 (2019): 1492.

[181] C. Brando. “Potential Applications of Liquid Biopsy in Immunotherapy: Role of Exosomes, Micrornas and Plasma Expression Levels of Immune Checkpoints in Patients With Solid Tumors” (PhD diss., University of Palermo, 2023), https://iris.unipa.it/handle/10447/595093.

[182] P. Jayashree, M. Kalpita, T. Judith, A. S. Singh, and K. Ashwin, “Role of MicroRNA in Hypoxic Tumours and Their Potential as Biomarkers for Early Detection of Cancer,” Current Molecular Medicine 24, no. 5 (2024): 525-536.

[183] N. Mukerjee, S. Nag, B. Bhattacharya, et al., “Clinical Impact of Epithelial-Mesenchymal Transition for Cancer Therapy,” Clinical and Translational Discovery 4, no. 1 (2024): e260.

[184] M. C. Borlongan and H. Wang, “Profiling and Targeting Cancer Stem Cell Signaling Pathways for Cancer Therapeutics,” Frontiers in Cell and Developmental Biology 11 (2023): 1125174.

[185] S. R. Gameiro, J. Strauss, J. L. Gulley, and J. Schlom, “Preclinical and Clinical Studies of Bintrafusp Alfa, a Novel Bifunctional Anti-PD-L1/TGFβRII Agent: Current Status,” Experimental Biology and Medicine 247, no. 13 (2022): 1124-1134.

[186] Y. Hu, F. Shen, X. Yang, et al., “Single-Cell Sequencing Technology Applied to Epigenetics for the Study of Tumor Heterogeneity,” Clinical Epigenetics 15, no. 1 (2023): 161.

[187] M. Pawlicka, E. Gumbarewicz, E. Błaszczak, and A. Stepulak, “Transcription Factors and Markers Related to Epithelial-Mesenchymal Transition and Their Role in Resistance to Therapies in Head and Neck Cancers,” Cancers 16, no. 7 (2024): 1354.

[188] A. M. Johansen, S. D. Forsythe, C. T. McGrath, et al., “TGFβ in Pancreas and Colorectal Cancer: Opportunities to Overcome Therapeutic Resistance,” Clinical Cancer Research 30, no. 17 (2024): 3676-3687.

[189] M. G. Cerrito and E. Grassilli, “Identifying Novel Actionable Targets in Colon Cancer,” Biomedicines 9, no. 5 (2021): 579.

[190] L. Kumari, L. Mishra, Y. Sharma, et al., “NOTCH Signaling Pathway: Occurrence, Mechanism, and NOTCH-Directed Therapy for the Management of Cancer,” Cancer Biotherapy & Radiopharmaceuticals 39, no. 1 (2024): 19-34.

[191] H. Zhu and X. Liu, “Advances of Tumorigenesis, Diagnosis at Early Stage, and Cellular Immunotherapy in Gastrointestinal Malignancies,” Frontiers in Oncology 11 (2021): 666340.

[192] M. Vigolo, C. Urech, S. Lamy, et al., “The Efficacy of CB-103, a First-in-Class Transcriptional Notch Inhibitor, in Preclinical Models of Breast Cancer,” Cancers 15, no. 15 (2023): 3957.

[193] A. Testa, E. Venturelli, and M. F. Brizzi, “Extracellular Vesicles as a Novel Liquid Biopsy-Based Diagnosis for the Central Nervous System, Head and Neck, Lung, and Gastrointestinal Cancers: Current and Future Perspectives,” Cancers 13, no. 11 (2021): 2792.

[194] S. H. Strand, B. Rivero-Gutiérrez, K. E. Houlahan, et al., “DCIS Genomic Signatures Define Biology and Correlate With Clinical Outcome: A Human Tumor Atlas Network (HTAN) Analysis of TBCRC 038 and RAHBT Cohorts,” preprint, BioRxiv, June 23, 2023, https://doi.org/10.1101/2021.06.16.448585.

[195] B. Küçükkaraduman, “Multiomics Approaches to Overcome Drug Resistance in Cancer” (PhD diss., Bilkent Universitesi, 2021), https://www.proquest.com/openview/9e3fdb9155c98e0f271c33a69edd762c/1?pq-origsite=gscholar&cbl=2026366&diss=y.

[196] I. Cavallari, F. Ciccarese, E. Sharova, et al., “The miR-200 Family of MicroRNAs: Fine Tuners of Epithelial-Mesenchymal Transition and Circulating Cancer Biomarkers,” Cancers 13, no. 23 (2021): 5874.

[197] Á. Gasparics and A. Sebe, “Forward Genetic Screens as Tools to Investigate Role and Mechanisms of EMT in Cancer,” Cancers 14, no. 23 (2022): 5928.

[198] M. Markouli, D. Strepkos, E. K. Basdra, A. G. Papavassiliou, and C. Piperi, “Prominent Role of Histone Modifications in the Regulation of Tumor Metastasis,” International Journal of Molecular Sciences 22, no. 5 (2021): 2778.

[199] V. Roman, M. Mihaila, N. Radu, S. Marineata, C. C. Diaconu, and M. Bostan, “Cell Culture Model Evolution and Its Impact on Improving Therapy Efficiency in Lung Cancer,” Cancers 15, no. 20 (2023): 4996.

[200] R. Subbarayan, D. Srinivasan, S. Sadullah Usmani, et al., “Molecular Insights on Eltrombopag: Potential Mitogen Stimulants, Angiogenesis, and Therapeutic Radioprotectant Through TPO-R Activation,” Platelets 35, no. 1 (2024): 2359028.

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