{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T19:48:10Z","timestamp":1773344890617,"version":"3.50.1"},"reference-count":117,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Malignant pleural mesothelioma (PM) is a highly aggressive disease of the lung pleura associated with poor prognosis. Despite advances in improving the clinical management of this malignancy, there is no effective chemotherapy for refractory or relapsing PM. The acquisition of resistance to standard and targeted therapy in this disease is a foremost concern; therefore, a deeper understanding of the complex factors surrounding the emergence of drug resistance is deemed necessary. In this review, we will present broad insights into various cellular and molecular concepts, accounting for the recalcitrance of PM to chemotherapy, including signaling networks regulating drug tolerance, drug resistance-associated proteins, genes, and miRNAs, as well as the critical role of cancer stem cells. Identification of the biological determinants and their associated mechanisms may provide a framework for the development of appropriate treatment.<\/jats:p>","DOI":"10.3390\/cancers17060979","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T04:29:18Z","timestamp":1741926558000},"page":"979","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["An Overview of Cellular and Molecular Determinants Regulating Chemoresistance in Pleural Mesothelioma"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8748-054X","authenticated-orcid":false,"given":"Lourdes","family":"Cortes-Dericks","sequence":"first","affiliation":[{"name":"Department of Biology, University of Hamburg, 20146 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4040-7211","authenticated-orcid":false,"given":"Domenico","family":"Galetta","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, San Giovanni Bosco Hospital, 10154 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.jtcvs.2009.11.072","article-title":"Prevalence of in Vitro Chemotherapeutic Drug Resistance in Primary Malignant Pleural Mesothelioma: Result in a Cohort of 203 Resection Specimens","volume":"140","author":"Mujoomdar","year":"2010","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Mastromarino, M.G., Aprile, V., and Lucchi, M. (2023). Editorial: Advances in Malignant Pleural Mesothelioma: Diagnosis, Treatment, and Molecular Mechanisms. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1158416"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"402","DOI":"10.3322\/caac.21572","article-title":"Mesothelioma: Scientific Clues for Prevention, Diagnosis, and Therapy","volume":"69","author":"Carbone","year":"2019","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Rossini, M., Rizzo, P., Bononi, I., Clementz, A., Ferrari, R., Martini, F., and Tognon, M.G. (2018). New Perspectives on Diagnosis and Therapy of Malignant Pleural Mesothelioma. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00091"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"319","DOI":"10.21037\/asj-22-37","article-title":"An Update in Malignant Peritoneal Mesothelioma Diagnosis and Treatment\u2014A Narrative Review","volume":"3","author":"Newland","year":"2023","journal-title":"AME Surg. J."},{"key":"ref_6","first-page":"319","article-title":"Malignant Pleural Mesothelioma","volume":"110","author":"Neumann","year":"2013","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1038\/bjc.2017.269","article-title":"Evaluating the Effect of Immune Cells on the Outcome of Patients with Mesothelioma","volume":"117","author":"Chee","year":"2017","journal-title":"Br. J. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1080\/17476348.2019.1563488","article-title":"Immunotherapy Strategies for Mesothelioma\u2014The Role of Tumor Specific Neoantigens in a New Era of Precision Medicine","volume":"13","author":"Ye","year":"2019","journal-title":"Expert. Rev. Respir. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Nicolini, F., Mazza, M., Nicolini, F., and Mazza, M. (2021). The Immune System of Mesothelioma Patients: A Window of Opportunity for Novel Immunotherapies. Rare Diseases-Diagnostic and Therapeutic Odyssey, IntechOpen.","DOI":"10.5772\/intechopen.98617"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3892\/mco.2022.2522","article-title":"Novel Approaches for the Treatment of Unresectable Malignant Pleural Mesothelioma: A Focus on Immunotherapy and Target Therapy (Review)","volume":"16","author":"Rijavec","year":"2022","journal-title":"Mol. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1200\/OP.21.00426","article-title":"Management of Advanced Pleural Mesothelioma\u2014At the Crossroads","volume":"18","author":"Nowak","year":"2022","journal-title":"JCO Oncol. Pract."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"100323","DOI":"10.1016\/j.opresp.2024.100323","article-title":"Advances in Immunotherapy for Malignant Pleural Mesothelioma: From Emerging Strategies to Translational Insights","volume":"6","year":"2024","journal-title":"Open Respir. Arch."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"TPS8602","DOI":"10.1200\/JCO.2023.41.16_suppl.TPS8602","article-title":"Neoadjuvant Immunotherapy in Sarcomatoid Mesothelioma (Alliance A082101)","volume":"41","author":"Mansfield","year":"2023","journal-title":"JCO J. Clin. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Nicolini, F., Bocchini, M., Bronte, G., Delmonte, A., Guidoboni, M., Crin\u00f2, L., and Mazza, M. (2019). Malignant Pleural Mesothelioma: State-of-the-Art on Current Therapies and Promises for the Future. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.01519"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1056\/NEJMra1912719","article-title":"Perspectives on the Treatment of Malignant Pleural Mesothelioma","volume":"385","author":"Janes","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.ctrv.2015.05.001","article-title":"The Established and Future Biomarkers of Malignant Pleural Mesothelioma","volume":"41","author":"Panou","year":"2015","journal-title":"Cancer Treat. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e161","DOI":"10.1016\/S1470-2045(18)30100-1","article-title":"Novel Therapies for Malignant Pleural Mesothelioma","volume":"19","author":"Scherpereel","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0140-6736(20)32714-8","article-title":"First-Line Nivolumab plus Ipilimumab in Unresectable Malignant Pleural Mesothelioma (CheckMate 743): A Multicentre, Randomised, Open-Label, Phase 3 Trial","volume":"397","author":"Baas","year":"2021","journal-title":"Lancet"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Cedres, S., Valdivia, A., Iranzo, P., Callejo, A., Pardo, N., Navarro, A., Martinez-Marti, A., Assaf-Pastrana, J.D., Felip, E., and Garrido, P. (2023). Current State-of-the-Art Therapy for Malignant Pleural Mesothelioma and Future Options Centered on Immunotherapy. Cancers, 15.","DOI":"10.3390\/cancers15245787"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Chen, S.-H., and Chang, J.-Y. (2019). New Insights into Mechanisms of Cisplatin Resistance: From Tumor Cell to Microenvironment. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20174136"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"303","DOI":"10.2147\/JEP.S267383","article-title":"Advances in Our Understanding of the Molecular Mechanisms of Action of Cisplatin in Cancer Therapy","volume":"13","author":"Tchounwou","year":"2021","journal-title":"JEP J. Exp. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S51","DOI":"10.3816\/CLC.2004.s.003","article-title":"Pharmacology and Mechanism of Action of Pemetrexed","volume":"5","author":"Adjei","year":"2004","journal-title":"Clin. Lung Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.21037\/tlcr.2019.10.14","article-title":"Mechanisms of Resistance to Pemetrexed in Non-Small Cell Lung Cancer","volume":"8","author":"Liang","year":"2019","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_24","first-page":"141","article-title":"Drug Resistance and Combating Drug Resistance in Cancer","volume":"2","author":"Wang","year":"2019","journal-title":"CDR Cancer Drug Resist."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ramos, A., Sadeghi, S., and Tabatabaeian, H. (2021). Battling Chemoresistance in Cancer: Root Causes and Strategies to Uproot Them. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179451"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.3390\/cancers6031769","article-title":"Drug Resistance in Cancer: An Overview","volume":"6","author":"Housman","year":"2014","journal-title":"Cancers"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4008","DOI":"10.18632\/oncotarget.14021","article-title":"Chemoresistance and Targeted Therapies in Ovarian and Endometrial Cancers","volume":"8","author":"Brasseur","year":"2016","journal-title":"Oncotarget"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"339","DOI":"10.15171\/apb.2017.041","article-title":"The Different Mechanisms of Cancer Drug Resistance: A Brief Review","volume":"7","author":"Mansoori","year":"2017","journal-title":"Adv. Pharm. Bull."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Cree, I.A., and Charlton, P. (2017). Molecular Chess? Hallmarks of Anti-Cancer Drug Resistance. BMC Cancer, 17.","DOI":"10.1186\/s12885-016-2999-1"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e1291","DOI":"10.1002\/cnr2.1291","article-title":"Molecular and Cellular Paradigms of Multidrug Resistance in Cancer","volume":"5","author":"Vaidya","year":"2022","journal-title":"Cancer Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s11010-008-9722-8","article-title":"Chemoresistance in Gliomas","volume":"312","author":"Lu","year":"2008","journal-title":"Mol. Cell Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"27","DOI":"10.21037\/pcm-21-12","article-title":"Asbestos-Induced Chronic Inflammation in Malignant Pleural Mesothelioma and Related Therapeutic Approaches-a Narrative Review","volume":"4","author":"Zolondick","year":"2021","journal-title":"Precis. Cancer Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"132","DOI":"10.4161\/cc.11.1.18474","article-title":"Butein Impairs the Protumorigenic Activity of Malignant Pleural Mesothelioma Cells","volume":"11","author":"Cioce","year":"2012","journal-title":"Cell Cycle"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3148","DOI":"10.1038\/onc.2011.485","article-title":"SASP Mediates Chemoresistance and Tumor-Initiating-Activity of Mesothelioma Cells","volume":"31","author":"Canino","year":"2012","journal-title":"Oncogene"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"12637","DOI":"10.18632\/oncotarget.3703","article-title":"A STAT3-NFkB\/DDIT3\/CEBP\u03b2 Axis Modulates ALDH1A3 Expression in Chemoresistant Cell Subpopulations","volume":"6","author":"Canino","year":"2015","journal-title":"Oncotarget"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.lungcan.2018.03.022","article-title":"Loss of C\/EBP-\u03b2 LIP Drives Cisplatin Resistance in Malignant Pleural Mesothelioma","volume":"120","author":"Kopecka","year":"2018","journal-title":"Lung Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e1167","DOI":"10.1038\/cddis.2014.136","article-title":"Autocrine CSF-1R Signaling Drives Mesothelioma Chemoresistance via AKT Activation","volume":"5","author":"Cioce","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1200\/JCO.2005.11.890","article-title":"Critical Update and Emerging Trends in Epidermal Growth Factor Receptor Targeting in Cancer","volume":"23","author":"Baselga","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.lungcan.2020.12.028","article-title":"Expression of EGFR and Conformational Forms of EGFR in Malignant Pleural Mesothelioma and Its Impact on Survival","volume":"153","author":"Chia","year":"2021","journal-title":"Lung Cancer"},{"key":"ref_40","first-page":"2401","article-title":"Sensitivity to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Requires E-Cadherin in Esophageal Cancer and Malignant Pleural Mesothelioma","volume":"33","author":"Xin","year":"2013","journal-title":"Anticancer. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/nature03098","article-title":"Intrinsic Tumour Suppression","volume":"432","author":"Lowe","year":"2004","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"13021","DOI":"10.1074\/jbc.M709698200","article-title":"Mammalian Target of Rapamycin Contributes to the Acquired Apoptotic Resistance of Human Mesothelioma Multicellular Spheroids","volume":"283","author":"Barbone","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Barbone, D., Follo, C., Echeverry, N., Gerbaudo, V.H., Klabatsa, A., Bueno, R., Felley-Bosco, E., and Broaddus, V.C. (2015). Autophagy Correlates with the Therapeutic Responsiveness of Malignant Pleural Mesothelioma in 3D Models. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0134825"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Zeng, R., and Dong, J. (2021). The Hippo Signaling Pathway in Drug Resistance in Cancer. Cancers, 13.","DOI":"10.3390\/cancers13020318"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.trecan.2019.02.010","article-title":"YAP\/TAZ Signaling and Resistance to Cancer Therapy","volume":"5","author":"Nguyen","year":"2019","journal-title":"Trends Cancer"},{"key":"ref_46","first-page":"3949","article-title":"Role of YAP in Lung Cancer Resistance to Cisplatin","volume":"16","author":"Song","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e18330","DOI":"10.1111\/jcmm.18330","article-title":"YAP\/TAZ-TEAD Signalling Axis: A New Therapeutic Target in Malignant Pleural Mesothelioma","volume":"28","author":"Papavassiliou","year":"2024","journal-title":"J. Cell. Mol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"39861","DOI":"10.18632\/oncotarget.9515","article-title":"Inhibition of FGF\/FGFR Autocrine Signaling in Mesothelioma with the FGF Ligand Trap, FP-1039\/GSK3052230","volume":"7","author":"Blackwell","year":"2016","journal-title":"Oncotarget"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.7150\/jca.40531","article-title":"FGF\/FGFR Signaling Pathway Involved Resistance in Various Cancer Types","volume":"11","author":"Zhou","year":"2020","journal-title":"J. Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"S153","DOI":"10.1016\/j.jtho.2021.01.175","article-title":"MA06.04 FGF5 Expression in Malignant Pleural Mesothelioma: Impact on Cell Growth, Cisplatin Resistance and Patient Survival","volume":"16","author":"Grusch","year":"2021","journal-title":"J. Thorac. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Staumont, B., Jamakhani, M., Costa, C., Vandermeers, F., Sriramareddy, S.N., Redout\u00e9, G., Mascaux, C., Delvenne, P., Hubert, P., and Safari, R. (2020). TGF\u03b1 Promotes Chemoresistance of Malignant Pleural Mesothelioma. Cancers, 12.","DOI":"10.3390\/cancers12061484"},{"key":"ref_52","first-page":"407","article-title":"Antioxidant Role of Metallothioneins: A Comparative Overview","volume":"46","author":"Viarengo","year":"2000","journal-title":"Cell. Mol. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1039\/C8MT00165K","article-title":"Metallothionein Diversity and Distribution in the Tree of Life: A Multifunctional Protein","volume":"10","author":"Ziller","year":"2018","journal-title":"Metallomics"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Borchert, S., Suckrau, P.-M., Walter, R.F.H., Wessolly, M., Mairinger, E., Steinborn, J., Hegedus, B., Hager, T., Herold, T., and Eberhardt, W.E.E. (2020). Impact of Metallothionein-Knockdown on Cisplatin Resistance in Malignant Pleural Mesothelioma. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-75807-x"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"22254","DOI":"10.18632\/oncotarget.24962","article-title":"Immunohistochemically Detectable Metallothionein Expression in Malignant Pleural Mesotheliomas Is Strongly Associated with Early Failure to Platin-Based Chemotherapy","volume":"9","author":"Mairinger","year":"2018","journal-title":"Oncotarget"},{"key":"ref_56","first-page":"220","article-title":"Thymidylate Synthase: A Critical Target for Cancer Chemotherapy","volume":"1","author":"Rose","year":"2002","journal-title":"Clin. Color. Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1002\/ijc.11221","article-title":"Overexpression of Thymidylate Synthase Mediates Desensitization for 5-Fluorouracil of Tumor Cells","volume":"106","author":"Saga","year":"2003","journal-title":"Int. J. Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Sato, Y., Tomita, M., Soga, T., Ochiai, A., and Makinoshima, H. (2021). Upregulation of Thymidylate Synthase Induces Pemetrexed Resistance in Malignant Pleural Mesothelioma. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.718675"},{"key":"ref_59","first-page":"33","article-title":"Interaction and Cross-Resistance of Cisplatin and Pemetrexed in Malignant Pleural Mesothelioma Cell Lines","volume":"28","author":"Takiguchi","year":"2012","journal-title":"Oncol. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.jare.2018.03.005","article-title":"Synopsis of Arachidonic Acid Metabolism: A Review","volume":"11","author":"Hanna","year":"2018","journal-title":"J. Adv. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1186\/s13046-021-02118-y","article-title":"Arachidonic Acid Drives Adaptive Responses to Chemotherapy-Induced Stress in Malignant Mesothelioma","volume":"40","author":"Cioce","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00280-017-3473-8","article-title":"The Promise and Challenges of Exploiting the Proton-Coupled Folate Transporter for Selective Therapeutic Targeting of Cancer","volume":"81","author":"Matherly","year":"2018","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1093\/annonc\/mdx499","article-title":"Role of Proton-Coupled Folate Transporter in Pemetrexed Resistance of Mesothelioma: Clinical Evidence and New Pharmacological Tools","volume":"28","author":"Giovannetti","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/s41416-020-0912-9","article-title":"Impact of Hypoxia on Chemoresistance of Mesothelioma Mediated by the Proton-Coupled Folate Transporter, and Preclinical Activity of New Anti-LDH-A Compounds","volume":"123","author":"Sciarrillo","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1038\/sj.onc.1201861","article-title":"BAP1: A Novel Ubiquitin Hydrolase Which Binds to the BRCA1 RING Finger and Enhances BRCA1-Mediated Cell Growth Suppression","volume":"16","author":"Jensen","year":"1998","journal-title":"Oncogene"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1097\/PAT.0b013e32835d0efb","article-title":"Tumours Associated with BAP1 Mutations","volume":"45","author":"Murali","year":"2013","journal-title":"Pathology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1158\/1078-0432.CCR-20-4037","article-title":"Alterations in BAP1 Are Associated with Cisplatin Resistance through Inhibition of Apoptosis in Malignant Pleural Mesothelioma","volume":"27","author":"Oehl","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Guazzelli, A., Meysami, P., Bakker, E., Demonacos, C., Giordano, A., Krstic-Demonacos, M., and Mutti, L. (2019). BAP1 Status Determines the Sensitivity of Malignant Mesothelioma Cells to Gemcitabine Treatment. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020429"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Berx, G., and van Roy, F. (2009). Involvement of Members of the Cadherin Superfamily in Cancer. Cold Spring Harb. Perspect. Biol., 1.","DOI":"10.1101\/cshperspect.a003129"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"6920","DOI":"10.1038\/onc.2008.343","article-title":"Cadherins and Cancer: How Does Cadherin Dysfunction Promote Tumor Progression?","volume":"27","author":"Jeanes","year":"2008","journal-title":"Oncogene"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5522","DOI":"10.1038\/onc.2017.147","article-title":"E-Cadherin Expression Is Correlated with Focal Adhesion Kinase Inhibitor Resistance in Merlin-Negative Malignant Mesothelioma Cells","volume":"36","author":"Kato","year":"2017","journal-title":"Oncogene"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1159\/000149782","article-title":"Acquisition of Cisplatin-Resistance in Malignant Mesothelioma Cells Abrogates Na+,K+,2Cl(-)-Cotransport Activity and Cisplatin-Induced Early Membrane Blebbing","volume":"22","author":"Janson","year":"2008","journal-title":"Cell Physiol. Biochem."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Corazzari, M., Gagliardi, M., Fimia, G.M., and Piacentini, M. (2017). Endoplasmic Reticulum Stress, Unfolded Protein Response, and Cancer Cell Fate. Front. Oncol., 7.","DOI":"10.3389\/fonc.2017.00078"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41416-018-0145-3","article-title":"Increased Sensitivity to Apoptosis upon Endoplasmic Reticulum Stress-Induced Activation of the Unfolded Protein Response in Chemotherapy-Resistant Malignant Pleural Mesothelioma","volume":"119","author":"Xu","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1042\/BJ20121323","article-title":"YB-1: Oncoprotein, Prognostic Marker and Therapeutic Target?","volume":"449","author":"Lasham","year":"2013","journal-title":"Biochem. J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"216395","DOI":"10.1016\/j.canlet.2023.216395","article-title":"Targeting YB-1 via Entinostat Enhances Cisplatin Sensitivity of Pleural Mesothelioma in Vitro and in Vivo","volume":"574","author":"Schelch","year":"2023","journal-title":"Cancer Lett."},{"key":"ref_77","first-page":"332","article-title":"Role of MicroRNAs in Chemoresistance","volume":"3","author":"Magee","year":"2015","journal-title":"Ann. Transl. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s13148-018-0587-8","article-title":"The Role and Mechanisms of Action of MicroRNAs in Cancer Drug Resistance","volume":"11","author":"Si","year":"2019","journal-title":"Clin. Epigenetics"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.omtn.2017.07.001","article-title":"MicroRNA-31 Regulates Chemosensitivity in Malignant Pleural Mesothelioma","volume":"8","author":"Moody","year":"2017","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.3892\/or.2014.3481","article-title":"MiR-379\/411 Cluster Regulates IL-18 and Contributes to Drug Resistance in Malignant Pleural Mesothelioma","volume":"32","author":"Yamamoto","year":"2014","journal-title":"Oncol. Rep."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.3892\/ijo.2016.3358","article-title":"Differential MicroRNA Expression Profiling of Mesothelioma and Expression Analysis of MiR-1 and MiR-214 in Mesothelioma","volume":"48","author":"Amatya","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Xiao, H., Liu, Y., Liang, P., Wang, B., Tan, H., Zhang, Y., Gao, X., and Gao, J. (2018). TP53TG1 Enhances Cisplatin Sensitivity of Non-Small Cell Lung Cancer Cells through Regulating MiR-18a\/PTEN Axis. Cell Biosci., 8.","DOI":"10.1186\/s13578-018-0221-7"},{"key":"ref_83","first-page":"4161","article-title":"Inhibition of MiR-18a-3p Reduces Proliferation of Mesothelioma Cells and Sensitizes Them to Cisplatin","volume":"19","author":"Suzuki","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"10001","DOI":"10.1002\/jcb.28283","article-title":"MiR-186 Inhibits Proliferation, Migration, and Epithelial-Mesenchymal Transition in Breast Cancer Cells by Targeting Twist1","volume":"120","author":"Sun","year":"2019","journal-title":"J. Cell Biochem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1093\/carcin\/bgw013","article-title":"PAQR3 Enhances Twist1 Degradation to Suppress Epithelial\u2013Mesenchymal Transition and Metastasis of Gastric Cancer Cells","volume":"37","author":"Guo","year":"2016","journal-title":"Carcinogenesis"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1002\/ar.20802","article-title":"Gene Expression Profiling in TWIST-Depleted Gastric Cancer Cells","volume":"292","author":"Feng","year":"2009","journal-title":"Anat. Rec."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"814","DOI":"10.20517\/cdr.2022.56","article-title":"Butein-Instigated MiR-186-5p-Dependent Modulation of TWIST1 Affects Resistance to Cisplatin and Bioenergetics of Malignant Pleural Mesothelioma Cells","volume":"5","author":"Cioce","year":"2022","journal-title":"Cancer Drug Resist."},{"key":"ref_88","first-page":"921","article-title":"Overcoming Multidrug Resistance in Human Lung Cancer with Novel Benzo[a]Quinolizin-4-Ones","volume":"31","author":"Kanintronkul","year":"2011","journal-title":"Anticancer. Res."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Emran, T.B., Shahriar, A., Mahmud, A.R., Rahman, T., Abir, M.H., Siddiquee, M.F.-R., Ahmed, H., Rahman, N., Nainu, F., and Wahyudin, E. (2022). Multidrug Resistance in Cancer: Understanding Molecular Mechanisms, Immunoprevention and Therapeutic Approaches. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.891652"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1080\/15384047.2017.1415677","article-title":"Micro-RNA149 Confers Taxane Resistance to Malignant Mesothelioma Cells via Regulation of P-Glycoprotein Expression","volume":"19","author":"Kenworthy","year":"2018","journal-title":"Cancer Biol. Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1023\/A:1012292230480","article-title":"The Expression of P-Glycoprotein and Multidrug Resistance Proteins 1 and 2 (MRP1 and MRP2) in Human Malignant Mesothelioma","volume":"12","author":"Soini","year":"2001","journal-title":"Ann. Oncol."},{"key":"ref_92","first-page":"1193","article-title":"Tumour Suppressor MicroRNAs Contribute to Drug Resistance in Malignant Pleural Mesothelioma by Targeting Anti-Apoptotic Pathways","volume":"2","author":"Williams","year":"2019","journal-title":"Cancer Drug Resist."},{"key":"ref_93","first-page":"517","article-title":"MiR-186 Reverses Cisplatin Resistance and Inhibits the Formation of the Glioblastoma-Initiating Cell Phenotype by Degrading Yin Yang 1 in Glioblastoma","volume":"43","author":"Li","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3417","DOI":"10.1039\/C6MB00576D","article-title":"MiR-186 Regulates Chemo-Sensitivity to Paclitaxel via Targeting MAPT in Non-Small Cell Lung Cancer (NSCLC)","volume":"12","author":"Ye","year":"2016","journal-title":"Mol. Biosyst."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"147","DOI":"10.4149\/neo_2019_190511N420","article-title":"MiR-186-5p Targeting SIX1 Inhibits Cisplatin Resistance in Non-Small-Cell Lung Cancer Cells (NSCLCs)","volume":"67","author":"Liu","year":"2020","journal-title":"Neoplasma"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1038\/nature15748","article-title":"Epithelial-to-Mesenchymal Transition Is Not Required for Lung Metastasis but Contributes to Chemoresistance","volume":"527","author":"Fischer","year":"2015","journal-title":"Nature"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.2147\/OTT.S260391","article-title":"A Concise Review: The Role of Stem Cells in Cancer Progression and Therapy","volume":"14","author":"Hayat","year":"2021","journal-title":"Onco Targets Ther."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1186\/s13287-022-02856-6","article-title":"Drug Resistance in Cancer Therapy: The Pandora\u2019s Box of Cancer Stem Cells","volume":"13","author":"Rezayatmand","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1740936","DOI":"10.1155\/2016\/1740936","article-title":"Cancer Stem Cell Quiescence and Plasticity as Major Challenges in Cancer Therapy","volume":"2016","author":"Chen","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"5416923","DOI":"10.1155\/2018\/5416923","article-title":"Cancer Stem Cells (CSCs) in Drug Resistance and Their Therapeutic Implications in Cancer Treatment","volume":"2018","author":"Phi","year":"2018","journal-title":"Stem Cells Int."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s12964-020-00627-5","article-title":"Drug Resistance and Cancer Stem Cells","volume":"19","author":"Li","year":"2021","journal-title":"Cell Commun. Signal."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"6357","DOI":"10.1038\/s41388-018-0405-y","article-title":"Differential Regulation of the Sphere Formation and Maintenance of Cancer-Initiating Cells of Malignant Mesothelioma via CD44 and ALK4 Signaling Pathways","volume":"37","author":"Ohno","year":"2018","journal-title":"Oncogene"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.bbrc.2010.12.054","article-title":"Identification of Cancer Stem Cell Markers in Human Malignant Mesothelioma Cells","volume":"404","author":"Ghani","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Pasdar, E.A., Smits, M., Stapelberg, M., Bajzikova, M., Stantic, M., Goodwin, J., Yan, B., Stursa, J., Kovarova, J., and Sachaphibulkij, K. (2015). Characterisation of Mesothelioma-Initiating Cells and Their Susceptibility to Anti-Cancer Agents. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0119549"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.bbrc.2012.02.054","article-title":"Characterization of Cancer Stem Cell Properties of CD24 and CD26-Positive Human Malignant Mesothelioma Cells","volume":"419","author":"Yamazaki","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_106","first-page":"437","article-title":"Putative Cancer Stem Cells in Malignant Pleural Mesothelioma Show Resistance to Cisplatin and Pemetrexed","volume":"37","author":"Carboni","year":"2010","journal-title":"Int. J. Oncol."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Cortes-Dericks, L., Froment, L., Boesch, R., Schmid, R.A., and Karoubi, G. (2014). Cisplatin-Resistant Cells in Malignant Pleural Mesothelioma Cell Lines Show ALDH(High)CD44(+) Phenotype and Sphere-Forming Capacity. BMC Cancer, 14.","DOI":"10.1186\/1471-2407-14-304"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.lungcan.2010.04.020","article-title":"Characterization of Side Population Cells in Human Malignant Mesothelioma Cell Lines","volume":"70","author":"Kai","year":"2010","journal-title":"Lung Cancer"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Melotti, A., Daga, A., Marubbi, D., Zunino, A., Mutti, L., and Corte, G. (2010). In Vitro and in Vivo Characterization of Highly Purified Human Mesothelioma Derived Cells. BMC Cancer, 10.","DOI":"10.1186\/1471-2407-10-54"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1093\/carcin\/bgr127","article-title":"Pleural Mesothelioma Side Populations Have a Precursor Phenotype","volume":"32","author":"Frei","year":"2011","journal-title":"Carcinogenesis"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Wu, L., Blum, W., Zhu, C.-Q., Yun, Z., Pecze, L., Kohno, M., Chan, M.-L., Zhao, Y., Felley-Bosco, E., and Schwaller, B. (2018). Putative Cancer Stem Cells May Be the Key Target to Inhibit Cancer Cell Repopulation between the Intervals of Chemoradiation in Murine Mesothelioma. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4354-1"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1002\/ijc.32419","article-title":"Wnt\/IL-1\u03b2\/IL-8 Autocrine Circuitries Control Chemoresistance in Mesothelioma Initiating Cells by Inducing ABCB5","volume":"146","author":"Milosevic","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"34495","DOI":"10.18632\/oncotarget.26130","article-title":"Transglutaminase Is a Mesothelioma Cancer Stem Cell Survival Protein That Is Required for Tumor Formation","volume":"9","author":"Adhikary","year":"2018","journal-title":"Oncotarget"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Sun, X., Lv, X., Yan, Y., Zhao, Y., Ma, R., He, M., and Wei, M. (2020). Hypoxia-Mediated Cancer Stem Cell Resistance and Targeted Therapy. Biomed. Pharmacother., 130.","DOI":"10.1016\/j.biopha.2020.110623"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Kim, M.-C., Hwang, S.-H., Kim, N.-Y., Lee, H.-S., Ji, S., Yang, Y., and Kim, Y. (2018). Hypoxia Promotes Acquisition of Aggressive Phenotypes in Human Malignant Mesothelioma. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4720-z"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"121","DOI":"10.32471\/exp-oncology.2312-8852.vol-44-no-2.18045","article-title":"Chemoresistance related to hypoxia adaptation in mesothelioma cells from tumor spheroids","volume":"44","author":"Endoh","year":"2022","journal-title":"Exp. Oncol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"574","DOI":"10.21037\/tlcr.2018.04.10","article-title":"Current Chemotherapy Strategies in Malignant Pleural Mesothelioma","volume":"7","author":"Baas","year":"2018","journal-title":"Transl. Lung Cancer Res."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/6\/979\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:53:24Z","timestamp":1760028804000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/6\/979"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,14]]},"references-count":117,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["cancers17060979"],"URL":"https:\/\/doi.org\/10.3390\/cancers17060979","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,14]]}}}