Mechanisms of Chemoresistance in Solid and Hematologic Malignancies: Challenges and Future Perspectives

• Badiaa Batlamous

  MOHAMMED V UNIVERSITY, RABAT, Morocco

• Boutaina Elgharbaoui

  Mohammed V University , Mohammed V University

• Imane Bensalim

  Mohammed VI Center for Research and Innovation (CM6RI) , Mohammed VI Center for Research and Innovation (CM6RI)

• Mohamed Khalis

  Mohammed VI Center for Research and Innovation (CM6RI) , Mohammed VI Center for Research and Innovation (CM6RI)

Chemotherapy is a foundational element in cancer therapy; however, the development of resistance to antineoplastic agents presents a significant challenge to achieving enduring therapeutic triumphs. The acquisition of drug resistance by malignant cells is the result of a complex interplay between inherent and acquired mechanisms. This phenomenon leads to a reduction in pharmacological effectiveness and contributes to treatment failure. This review investigates the primary mechanisms contributing to chemoresistance in specific malignancies, namely lung, pancreatic, and thyroid cancers, along with non-Hodgkin lymphoma. The primary focus of this research is on genetic modifications, interactions within the tumor microenvironment, and cellular adaptations at the molecular level. The present study places particular emphasis on the contributions of drug efflux pumps, DNA repair pathways, epithelial-mesenchymal transition (EMT), microRNAs, and the suppression of apoptosis in mediating this resistance. In addition, we examine promising approaches to counteract drug resistance, encompassing multi-agent regimens, inhibitors targeting specific molecular pathways, and innovative therapeutic modalities. A comprehensive understanding of these fundamental mechanisms is imperative for the development of sophisticated therapeutic interventions that not only improve patient outcomes but also effectively address resistance. The resistance pathways and prospective translational approaches discussed are drawn from both preclinical and clinical investigations, providing a thorough perspective. Keywords: The following terms are relevant to the study: chemoresistance, tumor microenvironment, molecular pathways, targeted therapy, and resistance mechanisms.

Abbasifarid, E., Sajjadi-Jazi, S. M., Beheshtian, M., Samimi, H., Larijani, B., & Haghpanah, V. (2019). The Role of ATP-Binding Cassette Transporters in the Chemoresistance of Anaplastic Thyroid Cancer: A Systematic Review. Endocrinology, 160(8), 2015–2023. https://doi.org/10.1210/en.2019-00241

Ansari, J., Shackelford, R. E., & El-Osta, H. (2016). Epigenetics in non-small cell lung cancer: from basics to therapeutics. Translational Lung Cancer Research, 5(2), 155–171. https://doi.org/10.21037/tlcr.2016.02.02

Assaraf, Y. G., Brozovic, A., Gonçalves, A. C., Jurkovicova, D., Linē, A., Machuqueiro, M., Saponara, S., Sarmento-Ribeiro, A. B., Xavier, C. P. R., & Vasconcelos, M. H. (2019). The multi-factorial nature of clinical multidrug resistance in cancer. Drug Resistance Updates, 46, 100645. https://doi.org/10.1016/j.drup.2019.100645

Bade, B. C., & Dela Cruz, C. S. (2020). Lung Cancer 2020. Clinics in Chest Medicine, 41(1), 1–24. https://doi.org/10.1016/j.ccm.2019.10.001

Bessho, Y., Oguri, T., Ozasa, H., Uemura, T., Sakamoto, H., Miyazaki, M., Maeno, K., Sato, S., & Ueda, R. (2009). ABCC10/MRP7 is associated with vinorelbine resistance in non-small cell lung cancer. Oncology Reports, 21(1), 263–268.

Bukowski, K., Kciuk, M., & Kontek, R. (2020). Mechanisms of Multidrug Resistance in Cancer Chemotherapy. International Journal of Molecular Sciences, 21(9), 3233. https://doi.org/10.3390/ijms21093233

Cai, W., Zeng, Q., Zhang, X., & Ruan, W. (2021). Trends Analysis of Non-Hodgkin Lymphoma at the National, Regional, and Global Level, 1990–2019: Results From the Global Burden of Disease Study 2019. Frontiers in Medicine, 8. https://doi.org/10.3389/fmed.2021.738693

Chaitanya Thandra, K., Barsouk, A., Saginala, K., Sukumar Aluru, J., & Barsouk, A. (2021). Epidemiology of lung cancer. Współczesna Onkologia, 25(1), 45–52. https://doi.org/10.5114/wo.2021.103829

Chen, P., Kuang, P., Wang, L., Li, W., Chen, B., Liu, Y., Wang, H., Zhao, S., Ye, L., Yu, F., He, Y., & Zhou, C. (2020). Mechanisms of drugs-resistance in small cell lung cancer: DNA-related, RNA-related, apoptosis-related, drug accumulation and metabolism procedure. Translational Lung Cancer Research, 9(3), 768–786. https://doi.org/10.21037/tlcr-19-547

Chonghaile, T. N., & Letai, A. (2008). Mimicking the BH3 domain to kill cancer cells. Oncogene, 27(S1), S149–S157. https://doi.org/10.1038/onc.2009.52

Cui, H., Arnst, K., Miller, D. D., & Li, W. (2020). Recent Advances in Elucidating Paclitaxel Resistance Mechanisms in Non-small Cell Lung Cancer and Strategies to Overcome Drug Resistance. Current Medicinal Chemistry, 27(39), 6573–6595. https://doi.org/10.2174/0929867326666191016113631

Cuomo, F., Giani, C., & Cobellis, G. (2022). The Role of the Kinase Inhibitors in Thyroid Cancers. Pharmaceutics, 14(5), 1040. https://doi.org/10.3390/pharmaceutics14051040

de Moura, A., Vuagnat, P., Renouf, B., Pierga, J.-Y., Loirat, D., Vaflard, P., Lafayolle de la Bruyère, C., Chaumard-Billotey, N., Hajjaji, N., Ladoire, S., Dabakuyo, S., Patsouris, A., Frenel, J. S., Nicolai, V., Alexandre, M., Dohollou, N., Grenier, J., Bourien, H., & Bidard, F.-C. (2023). Atezolizumab and paclitaxel as first line therapy in advanced triple-negative breast cancer patients included in the French early access program. Scientific Reports, 13(1), 13427. https://doi.org/10.1038/s41598-023-40569-9

DeRidder, L., Rubinson, D. A., Langer, R., & Traverso, G. (2022). The past, present, and future of chemotherapy with a focus on individualization of drug dosing. Journal of Controlled Release, 352, 840–860. https://doi.org/10.1016/j.jconrel.2022.10.043

de Sousa, V. M. L., & Carvalho, L. (2018). Heterogeneity in Lung Cancer. Pathobiology, 85(1–2), 96–107. https://doi.org/10.1159/000487440

Dzobo, K., Senthebane, D. A., Thomford, N. E., Rowe, A., Dandara, C., & Parker, M. I. (2018). Not Everyone Fits the Mold: Intratumor and Intertumor Heterogeneity and Innovative Cancer Drug Design and Development. OMICS: A Journal of Integrative Biology, 22(1), 17–34. https://doi.org/10.1089/omi.2017.0174

Espona-Fiedler, M., Patthey, C., Lindblad, S., Sarró, I., & Öhlund, D. (2024). Overcoming therapy resistance in pancreatic cancer: New insights and future directions. Biochemical Pharmacology, 229, 116492. https://doi.org/10.1016/j.bcp.2024.116492

Geisslinger, F., Müller, M., Vollmar, A. M., & Bartel, K. (2020). Targeting Lysosomes in Cancer as Promising Strategy to Overcome Chemoresistance—A Mini Review. Frontiers in Oncology, 10. https://doi.org/10.3389/fonc.2020.01156

Hanahan, D. (2022). Hallmarks of Cancer: New Dimensions. Cancer Discovery, 12(1), 31–46. https://doi.org/10.1158/2159-8290.CD-21-1059

Holohan, C., Van Schaeybroeck, S., Longley, D. B., & Johnston, P. G. (2013). Cancer drug resistance: an evolving paradigm. Nature Reviews Cancer, 13(10), 714–726. https://doi.org/10.1038/nrc3599

Housman, G., Byler, S., Heerboth, S., Lapinska, K., Longacre, M., Snyder, N., & Sarkar, S. (2014). Drug Resistance in Cancer: An Overview. Cancers, 6(3), 1769–1792. https://doi.org/10.3390/cancers6031769

Hua, X., Zhao, W., Pesatori, A. C., Consonni, D., Caporaso, N. E., Zhang, T., Zhu, B., Wang, M., Jones, K., Hicks, B., Song, L., Sampson, J., Wedge, D. C., Shi, J., & Landi, M. T. (2020). Genetic and epigenetic intratumor heterogeneity impacts prognosis of lung adenocarcinoma. Nature Communications, 11(1), 2459. https://doi.org/10.1038/s41467-020-16295-5

Inno, A., Stagno, A., & Gori, S. (2018). Schlafen-11 (SLFN11): a step forward towards personalized medicine in small-cell lung cancer? Translational Lung Cancer Research, 7(S4), S341–S345. https://doi.org/10.21037/tlcr.2018.11.06

Janet Wangari-Talbot, & Elizabeth Hopper-Borge. (2013). Drug Resistance Mechanisms in Non-Small Cell Lung Carcinoma. Journal of Cancer Research Updates, 2(4). https://doi.org/10.6000/1929-2279.2013.02.04.5

Jiang, Y., Redmond, D., Nie, K., Eng, K. W., Clozel, T., Martin, P., Tan, L., Melnick, A. M., Tam, W., & Elemento, O. (2014). Deep-sequencing reveals clonal evolution patterns and mutation events associated with relapse in B-cell lymphomas. Genome Biology, 15(8), 432. https://doi.org/10.1186/PREACCEPT-6612547881370092

Jordan, M. A., & Wilson, L. (2004). Microtubules as a target for anticancer drugs. Nature Reviews Cancer, 4(4), 253–265. https://doi.org/10.1038/nrc1317

Juskevicius, D., Lorber, T., Gsponer, J., Perrina, V., Ruiz, C., Stenner-Liewen, F., Dirnhofer, S., & Tzankov, A. (2016). Distinct genetic evolution patterns of relapsing diffuse large B-cell lymphoma revealed by genome-wide copy number aberration and targeted sequencing analysis. Leukemia, 30(12), 2385–2395. https://doi.org/10.1038/leu.2016.135

Kamisawa, T., Wood, L. D., Itoi, T., & Takaori, K. (2016). Pancreatic cancer. The Lancet, 388(10039), 73–85. https://doi.org/10.1016/S0140-6736(16)00141-0

Kar, A., Agarwal, S., Singh, A., Bajaj, A., & Dasgupta, U. (2024). Insights into molecular mechanisms of chemotherapy resistance in cancer. Translational Oncology, 42, 101901. https://doi.org/10.1016/j.tranon.2024.101901

Kaur, S., Smith, L. M., Patel, A., Menning, M., Watley, D. C., Malik, S. S., Krishn, S. R., Mallya, K., Aithal, A., Sasson, A. R., Johansson, S. L., Jain, M., Singh, S., Guha, S., Are, C., Raimondo, M., Hollingsworth, M. A., Brand, R. E., & Batra, S. K. (2017). A Combination of MUC5AC and CA19-9 Improves the Diagnosis of Pancreatic Cancer: A Multicenter Study. American Journal of Gastroenterology, 112(1), 172–183. https://doi.org/10.1038/ajg.2016.482

Khan, S. U., Fatima, K., Aisha, S., & Malik, F. (2024). Unveiling the mechanisms and challenges of cancer drug resistance. Cell Communication and Signaling, 22(1), 109. https://doi.org/10.1186/s12964-023-01302-1

Kim, J.-Y., & Lee, J.-Y. (2017). Targeting Tumor Adaption to Chronic Hypoxia: Implications for Drug Resistance, and How It Can Be Overcome. International Journal of Molecular Sciences, 18(9), 1854. https://doi.org/10.3390/ijms18091854

Kleeff, J., Korc, M., Apte, M., La Vecchia, C., Johnson, C. D., Biankin, A. V., Neale, R. E., Tempero, M., Tuveson, D. A., Hruban, R. H., & Neoptolemos, J. P. (2016). Pancreatic cancer. Nature Reviews Disease Primers, 2(1), 16022. https://doi.org/10.1038/nrdp.2016.22

Klener, P., & Klanova, M. (2020). Drug Resistance in Non-Hodgkin Lymphomas. International Journal of Molecular Sciences, 21(6), 2081. https://doi.org/10.3390/ijms21062081

Konstantinov, S. M., & Berger, M. R. (n.d.). Alkylating Agents. In Encyclopedia of Molecular Pharmacology (pp. 53–57). Springer Berlin Heidelberg. https://doi.org/10.1007/978-3-540-38918-7_178

Labrie, M., Brugge, J. S., Mills, G. B., & Zervantonakis, I. K. (2022). Therapy resistance: opportunities created by adaptive responses to targeted therapies in cancer. Nature Reviews Cancer, 22(6), 323–339. https://doi.org/10.1038/s41568-022-00454-5

Liu, R., Chen, Y., Liu, G., Li, C., Song, Y., Cao, Z., Li, W., Hu, J., Lu, C., & Liu, Y. (2020). PI3K/AKT pathway as a key link modulates the multidrug resistance of cancers. Cell Death & Disease, 11(9), 797. https://doi.org/10.1038/s41419-020-02998-6

Liu, X. (2025). SEMA6B promotes thyroid tumorigenesis and chemoresistance via WNT/β-catenin signaling in response to doxorubicin. American Journal of Cancer Research, 15(4), 1540–1558. https://doi.org/10.62347/BIUC4913

Lok, B. H., Gardner, E. E., Schneeberger, V. E., Ni, A., Desmeules, P., Rekhtman, N., de Stanchina, E., Teicher, B. A., Riaz, N., Powell, S. N., Poirier, J. T., & Rudin, C. M. (2017). PARP Inhibitor Activity Correlates with SLFN11 Expression and Demonstrates Synergy with Temozolomide in Small Cell Lung Cancer. Clinical Cancer Research, 23(2), 523–535. https://doi.org/10.1158/1078-0432.CCR-16-1040

Marino, F. Z., Bianco, R., Accardo, M., Ronchi, A., Cozzolino, I., Morgillo, F., Rossi, G., & Franco, R. (2019). Molecular heterogeneity in lung cancer: from mechanisms of origin to clinical implications. International Journal of Medical Sciences, 16(7), 981–989. https://doi.org/10.7150/ijms.34739

Miglietta, F., Iamartino, L., Palmini, G., Giusti, F., Marini, F., Iantomasi, T., & Brandi, M. L. (2023). Endocrine sequelae of hematopoietic stem cell transplantation: Effects on mineral homeostasis and bone metabolism. Frontiers in Endocrinology, 13. https://doi.org/10.3389/fendo.2022.1085315

Min, H.-Y., & Lee, H.-Y. (2021). Mechanisms of resistance to chemotherapy in non-small cell lung cancer. Archives of Pharmacal Research, 44(2), 146–164. https://doi.org/10.1007/s12272-021-01312-y

Mukhtar, F., Boffetta, P., Dabo, B., Park, J. Y., Tran, C. T. D., Tran, T. V., Tran, H. T.-T., Whitney, M., Risch, H. A., Le, L. C., Zheng, W., Shu, X.-O., & Luu, H. N. (2018). Disparities by race, age, and sex in the improvement of survival for lymphoma: Findings from a population-based study. PLOS ONE, 13(7), e0199745. https://doi.org/10.1371/journal.pone.0199745

Nassar, D., & Blanpain, C. (2016). Cancer Stem Cells: Basic Concepts and Therapeutic Implications. Annual Review of Pathology: Mechanisms of Disease, 11(1), 47–76. https://doi.org/10.1146/annurev-pathol-012615-044438

Nurgali, K., Jagoe, R. T., & Abalo, R. (2018). Editorial: Adverse Effects of Cancer Chemotherapy: Anything New to Improve Tolerance and Reduce Sequelae? Frontiers in Pharmacology, 9. https://doi.org/10.3389/fphar.2018.00245

Oguri, T., Ozasa, H., Uemura, T., Bessho, Y., Miyazaki, M., Maeno, K., Maeda, H., Sato, S., & Ueda, R. (2008). MRP7/ABCC10 expression is a predictive biomarker for the resistance to paclitaxel in non-small cell lung cancer. Molecular Cancer Therapeutics, 7(5), 1150–1155. https://doi.org/10.1158/1535-7163.MCT-07-2088

Olaussen, K. A., & Postel-Vinay, S. (2016). Predictors of chemotherapy efficacy in non-small-cell lung cancer: a challenging landscape. Annals of Oncology, 27(11), 2004–2016. https://doi.org/10.1093/annonc/mdw321

Pearce, M. C., Gamble, J. T., Kopparapu, P. R., O’Donnell, E. F., Mueller, M. J., Jang, H. S., Greenwood, J. A., Satterthwait, A. C., Tanguay, R. L., Zhang, X.-K., & Kolluri, S. K. (2018). Induction of apoptosis and suppression of tumor growth by Nur77-derived Bcl-2 converting peptide in chemoresistant lung cancer cells. Oncotarget, 9(40), 26072–26085. https://doi.org/10.18632/oncotarget.25437

Pljesa-Ercegovac, M., Savic-Radojevic, A., Matic, M., Coric, V., Djukic, T., Radic, T., & Simic, T. (2018). Glutathione Transferases: Potential Targets to Overcome Chemoresistance in Solid Tumors. International Journal of Molecular Sciences, 19(12), 3785. https://doi.org/10.3390/ijms19123785

Quiñonero, F., Mesas, C., Doello, K., Cabeza, L., Perazzoli, G., Jimenez-Luna, C., Rosa Rama, A., Melguizo, C., & Prados, J. (2019). The challenge of drug resistance in pancreatic ductal adenocarcinoma: a current overview. Cancer Biology & Medicine, 16(4), 688–699. https://doi.org/10.20892/j.issn.2095-3941.2019.0252

Rahib, L., Smith, B. D., Aizenberg, R., Rosenzweig, A. B., Fleshman, J. M., & Matrisian, L. M. (2014). Projecting Cancer Incidence and Deaths to 2030: The Unexpected Burden of Thyroid, Liver, and Pancreas Cancers in the United States. Cancer Research, 74(11), 2913–2921. https://doi.org/10.1158/0008-5472.CAN-14-0155

Ramos, A., Sadeghi, S., & Tabatabaeian, H. (2021). Battling Chemoresistance in Cancer: Root Causes and Strategies to Uproot Them. International Journal of Molecular Sciences, 22(17), 9451. https://doi.org/10.3390/ijms22179451

Rawla, P., Sunkara, T., & Gaduputi, V. (2019). Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors. World Journal of Oncology, 10(1), 10–27. https://doi.org/10.14740/wjon1166

Reshma, P. L., Unnikrishnan, B. S., Preethi, G. U., Syama, H. P., Archana, M. G., Remya, K., Shiji, R., Sreekutty, J., & Sreelekha, T. T. (2019). Overcoming drug-resistance in lung cancer cells by paclitaxel loaded galactoxyloglucan nanoparticles. International Journal of Biological Macromolecules, 136, 266–274. https://doi.org/10.1016/j.ijbiomac.2019.06.075

Riganti, C., & Contino, M. (2019). New Strategies to Overcome Resistance to Chemotherapy and Immune System in Cancer. International Journal of Molecular Sciences, 20(19), 4783. https://doi.org/10.3390/ijms20194783

Russo, M., Crisafulli, G., Sogari, A., Reilly, N. M., Arena, S., Lamba, S., Bartolini, A., Amodio, V., Magrì, A., Novara, L., Sarotto, I., Nagel, Z. D., Piett, C. G., Amatu, A., Sartore-Bianchi, A., Siena, S., Bertotti, A., Trusolino, L., Corigliano, M., … Bardelli, A. (2019). Adaptive mutability of colorectal cancers in response to targeted therapies. Science, 366(6472), 1473–1480. https://doi.org/10.1126/science.aav4474

Schürch, C. M., Federmann, B., Quintanilla-Martinez, L., & Fend, F. (2018). Tumor Heterogeneity in Lymphomas: A Different Breed. Pathobiology, 85(1–2), 130–145. https://doi.org/10.1159/000475530

Seib, C. D., & Sosa, J. A. (2019). Evolving Understanding of the Epidemiology of Thyroid Cancer. Endocrinology and Metabolism Clinics of North America, 48(1), 23–35. https://doi.org/10.1016/j.ecl.2018.10.002

Sharma, A., Patrick, B., Li, J., Sharma, R., Jeyabal, P. V. S., Reddy, P. M. R. V., Awasthi, S., & Awasthi, Y. C. (2006). Glutathione S-transferases as antioxidant enzymes: Small cell lung cancer (H69) cells transfected with hGSTA1 resist doxorubicin-induced apoptosis. Archives of Biochemistry and Biophysics, 452(2), 165–173. https://doi.org/10.1016/j.abb.2006.04.006

Sharma, S. V., Lee, D. Y., Li, B., Quinlan, M. P., Takahashi, F., Maheswaran, S., McDermott, U., Azizian, N., Zou, L., Fischbach, M. A., Wong, K.-K., Brandstetter, K., Wittner, B., Ramaswamy, S., Classon, M., & Settleman, J. (2010). A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell Subpopulations. Cell, 141(1), 69–80. https://doi.org/10.1016/j.cell.2010.02.027

Shen, W., Pang, H., Liu, J., Zhou, J., Zhang, F., Liu, L., Ma, N., Zhang, N., Zhang, H., & Liu, L. (2014). EpithelialMesenchymal Transition Contributes to Docetaxel Resistance in Human Non-Small Cell Lung Cancer. Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, 22(1), 47–55. https://doi.org/10.3727/096504014X14098532393473

SHIMOMURA, M., YAOI, T., ITOH, K., KATO, D., TERAUCHI, K., SHIMADA, J., & FUSHIKI, S. (2012). Drug resistance to paclitaxel is not only associated with ABCB1 mRNA expression but also with drug accumulation in intracellular compartments in human lung cancer cell lines. International Journal of Oncology, 40(4), 995–1004. https://doi.org/10.3892/ijo.2011.1297

Si, W., Shen, J., Zheng, H., & Fan, W. (2019). The role and mechanisms of action of microRNAs in cancer drug resistance. Clinical Epigenetics, 11(1), 25. https://doi.org/10.1186/s13148-018-0587-8

Siegel, R. L., Miller, K. D., & Jemal, A. (2018). Cancer statistics, 2018. CA: A Cancer Journal for Clinicians, 68(1), 7–30. https://doi.org/10.3322/caac.21442

Siegel, R. L., Miller, K. D., & Jemal, A. (2019). Cancer statistics, 2019. CA: A Cancer Journal for Clinicians, 69(1), 7–34. https://doi.org/10.3322/caac.21551

Stewart, D. J. (2007). Mechanisms of resistance to cisplatin and carboplatin. Critical Reviews in Oncology/Hematology, 63(1), 12–31. https://doi.org/10.1016/j.critrevonc.2007.02.001

Sun, C.-Y., Nie, J., Huang, J.-P., Zheng, G.-J., & Feng, B. (2019). Targeting STAT3 inhibition to reverse cisplatin resistance. Biomedicine & Pharmacotherapy, 117, 109135. https://doi.org/10.1016/j.biopha.2019.109135

Sun, Y., Hu, B., Wang, Q., Ye, M., Qiu, Q., Zhou, Y., Zeng, F., Zhang, X., Guo, Y., & Guo, L. (2018). Long non-coding RNA HOTTIP promotes BCL-2 expression and induces chemoresistance in small cell lung cancer by sponging miR-216a. Cell Death & Disease, 9(2), 85. https://doi.org/10.1038/s41419-017-0113-5

Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71(3), 209–249. https://doi.org/10.3322/caac.21660

Thomas, S., Quinn, B. A., Das, S. K., Dash, R., Emdad, L., Dasgupta, S., Wang, X.-Y., Dent, P., Reed, J. C., Pellecchia, M., Sarkar, D., & Fisher, P. B. (2013). Targeting the Bcl-2 family for cancer therapy. Expert Opinion on Therapeutic Targets, 17(1), 61–75. https://doi.org/10.1517/14728222.2013.733001

Townsend, D. M., & Tew, K. D. (2003). The role of glutathione-S-transferase in anti-cancer drug resistance. Oncogene, 22(47), 7369–7375. https://doi.org/10.1038/sj.onc.1206940

Wang, H., Chen, J., Zhang, S., Zheng, X., Xie, S., Mao, J., Cai, Y., Lu, X., Hu, L., Shen, J., Chai, K., & Chen, W. (2020). MiR-223 regulates autophagy associated with cisplatin resistance by targeting FBXW7 in human non-small cell lung cancer. Cancer Cell International, 20(1), 258. https://doi.org/10.1186/s12935-020-01284-x

Wu, J., Zhang, Y., Cheng, R., Gong, W., Ding, T., Zhai, Q., Wang, Y., Meng, B., & Sun, B. (2019). Expression of epithelial‐mesenchymal transition regulators TWIST , SLUG and SNAIL in follicular thyroid tumours may relate to widely invasive, poorly differentiated and distant metastasis. Histopathology, 74(5), 780–791. https://doi.org/10.1111/his.13778

Xu, H., Wang, W., Liu, X., Huang, W., Zhu, C., Xu, Y., Yang, H., Bai, J., & Geng, D. (2023). Targeting strategies for bone diseases: signaling pathways and clinical studies. Signal Transduction and Targeted Therapy, 8(1), 202. https://doi.org/10.1038/s41392-023-01467-8

Young, L. C., Campling, B. G., Cole, S. P., Deeley, R. G., & Gerlach, J. H. (2001). Multidrug resistance proteins MRP3, MRP1, and MRP2 in lung cancer: correlation of protein levels with drug response and messenger RNA levels. Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, 7(6), 1798–1804.

Yuan, M., Huang, L.-L., Chen, J.-H., Wu, J., & Xu, Q. (2019). The emerging treatment landscape of targeted therapy in non-small-cell lung cancer. Signal Transduction and Targeted Therapy, 4(1), 61. https://doi.org/10.1038/s41392-019-0099-9

Zagryazhskaya, A., & Zhivotovsky, B. (2014). miRNAs in lung cancer: A link to aging. Ageing Research Reviews, 17, 54–67. https://doi.org/10.1016/j.arr.2014.02.009

Zhang, Y., Xing, Z., Liu, T., Tang, M., Mi, L., Zhu, J., Wu, W., & Wei, T. (2022). Targeted therapy and drug resistance in thyroid cancer. European Journal of Medicinal Chemistry, 238, 114500. https://doi.org/10.1016/j.ejmech.2022.114500

Zhao, Y., Lu, H., Yan, A., Yang, Y., Meng, Q., Sun, L., Pang, H., Li, C., Dong, X., & Cai, L. (2013). ABCC3 as a marker for multidrug resistance in non-small cell lung cancer. Scientific Reports, 3(1), 3120. https://doi.org/10.1038/srep03120

Zhou, Y., Liu, H., Xue, R., Tang, W., & Zhang, S. (2018). BH3 Mimetic ABT-199 Enhances the Sensitivity of Gemcitabine in Pancreatic Cancer in vitro and in vivo. Digestive Diseases and Sciences, 63(12), 3367–3375. https://doi.org/10.1007/s10620-018-5253-7

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