{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T03:42:32Z","timestamp":1792899752495,"version":"4.5.0"},"reference-count":159,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T00:00:00Z","timestamp":1684800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Center of Poland","doi-asserted-by":"publisher","award":["2018\/31\/B\/NZ7\/02909"],"award-info":[{"award-number":["2018\/31\/B\/NZ7\/02909"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"National Science Center of Poland","doi-asserted-by":"publisher","award":["AIRC IG grant 24444"],"award-info":[{"award-number":["AIRC IG grant 24444"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007076","name":"Mesothelioma Applied Research Foundation, US, and by Italian Association for the Study of Cancer","doi-asserted-by":"publisher","award":["2018\/31\/B\/NZ7\/02909"],"award-info":[{"award-number":["2018\/31\/B\/NZ7\/02909"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007076","name":"Mesothelioma Applied Research Foundation, US, and by Italian Association for the Study of Cancer","doi-asserted-by":"publisher","award":["AIRC IG grant 24444"],"award-info":[{"award-number":["AIRC IG grant 24444"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Malignant Pleural Mesothelioma (MPM) is a rare neoplasm that is typically diagnosed in a locally advanced stage, making it not eligible for radical surgery and requiring systemic treatment. Chemotherapy with platinum compounds and pemetrexed has been the only approved standard of care for approximately 20 years, without any relevant therapeutic advance until the introduction of immune checkpoint inhibitors. Nevertheless, the prognosis remains poor, with an average survival of only 18 months. Thanks to a better understanding of the molecular mechanisms underlying tumor biology, targeted therapy has become an essential therapeutic option in several solid malignancies. Unfortunately, most of the clinical trials evaluating potentially targeted drugs for MPM have failed. This review aims to present the main findings of the most promising targeted therapies in MPM, and to explore possible reasons leading to treatments failures. The ultimate goal is to determine whether there is still a place for continued preclinical\/clinical research in this area.<\/jats:p>","DOI":"10.3390\/ijms24119165","type":"journal-article","created":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T01:29:26Z","timestamp":1684891766000},"page":"9165","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Target Therapy in Malignant Pleural Mesothelioma: Hope or Mirage?"],"prefix":"10.3390","volume":"24","author":[{"given":"Federica","family":"Borea","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090 Milan, Italy"},{"name":"Department of Medical Oncology, Amsterdam University Medical Centers, Location VUmc, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9525-4374","authenticated-orcid":false,"given":"Marika A.","family":"Franczak","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Amsterdam University Medical Centers, Location VUmc, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Department of Biochemistry, Medical University of Gdansk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Garcia","sequence":"additional","affiliation":[{"name":"Faculty of Experimental Science, Universidad Francisco de Vitoria, 28223 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Perrino","sequence":"additional","affiliation":[{"name":"IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Cordua","sequence":"additional","affiliation":[{"name":"IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0190-9414","authenticated-orcid":false,"given":"Ryszard T.","family":"Smolenski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Gdansk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5447-2877","authenticated-orcid":false,"given":"Godefridus J.","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Amsterdam University Medical Centers, Location VUmc, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Department of Biochemistry, Medical University of Gdansk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafal","family":"Dziadziuszko","sequence":"additional","affiliation":[{"name":"Department of Oncology and Radiotherapy and Early Phase Clinical Trials Centre, Medical University of Gdansk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando","family":"Santoro","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090 Milan, Italy"},{"name":"IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2274-1702","authenticated-orcid":false,"given":"Paolo A.","family":"Zucali","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090 Milan, Italy"},{"name":"IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7565-7504","authenticated-orcid":false,"given":"Elisa","family":"Giovannetti","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Amsterdam University Medical Centers, Location VUmc, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Fondazione Pisana per la Scienza, 56017 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,23]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/modpathol.2011.144","article-title":"Epithelial\u2013Mesenchymal Transition in Malignant Mesothelioma","volume":"25","author":"Fassina","year":"2012","journal-title":"Mod. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1200\/JCO.2003.11.136","article-title":"Phase III Study of Pemetrexed in Combination with Cisplatin versus Cisplatin Alone in Patients with Malignant Pleural Mesothelioma","volume":"21","author":"Vogelzang","year":"2003","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1200\/JCO.2005.04.3190","article-title":"Phase II Study of Pemetrexed Plus Carboplatin in Malignant Pleural Mesothelioma","volume":"24","author":"Ceresoli","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"875974","DOI":"10.3389\/fmed.2022.875974","article-title":"Overview of Checkpoint Inhibitors Mechanism of Action: Role of Immune-Related Adverse Events and Their Treatment on Progression of Underlying Cancer","volume":"9","author":"Iranzo","year":"2022","journal-title":"Front. Med."},{"key":"ref_6","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_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2147\/LCTT.S288535","article-title":"An Update on Emerging Therapeutic Options for Malignant Pleural Mesothelioma","volume":"13","author":"Davis","year":"2022","journal-title":"Lung Cancer Targets Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"105","DOI":"10.2217\/fon-2017-0524","article-title":"Precision Medicine Strategies in Oncology: Mixed Approaches to Matched Therapies","volume":"14","author":"Borcoman","year":"2018","journal-title":"Future Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.ctrv.2011.01.001","article-title":"Advances in the Biology of Malignant Pleural Mesothelioma","volume":"37","author":"Zucali","year":"2011","journal-title":"Cancer Treat. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1165\/ajrcmb.12.5.7742009","article-title":"The Role of Growth Factors and Cytokines in the Tumorigenesis and Immunobiology of Malignant Mesothelioma","volume":"12","author":"Fitzpatrick","year":"1995","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1378\/chest.08-2665","article-title":"Malignant Pleural Mesothelioma: An Update on Biomarkers and Treatment","volume":"136","author":"Ray","year":"2009","journal-title":"Chest"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1002\/path.824","article-title":"Vascular Endothelial Growth Factor Is an Autocrine Growth Factor in Human Malignant Mesothelioma","volume":"193","author":"Strizzi","year":"2001","journal-title":"J. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1016\/j.hoc.2005.09.008","article-title":"Antiangiogenic Therapies for Mesothelioma","volume":"19","author":"Dowell","year":"2005","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1186\/gb-2005-6-2-209","article-title":"The Vascular Endothelial Growth Factor (VEGF) Family: Angiogenic Factors in Health and Disease","volume":"6","author":"Holmes","year":"2005","journal-title":"Genome Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/nm0603-669","article-title":"The Biology of VEGF and Its Receptors","volume":"9","author":"Ferrara","year":"2003","journal-title":"Nat. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1042\/bst0311171","article-title":"VEGF Signalling: Integration and Multi-Tasking in Endothelial Cell Biology","volume":"31","author":"Zachary","year":"2003","journal-title":"Biochem. Soc. Trans."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.semcancer.2003.09.018","article-title":"Antiangiogenic Cancer Therapy","volume":"14","author":"Cao","year":"2004","journal-title":"Semin. Cancer Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1002\/(SICI)1096-9896(199909)189:1<72::AID-PATH401>3.0.CO;2-0","article-title":"Angiogenic Cytokines in Mesothelioma: A Study of VEGF, FGF-1 and -2, and TGF? Expression","volume":"189","author":"Weyler","year":"1999","journal-title":"J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s12964-022-00838-y","article-title":"Cancer Combination Therapies by Angiogenesis Inhibitors; a Comprehensive Review","volume":"20","author":"Ansari","year":"2022","journal-title":"Cell Commun. Signal."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1111\/j.1476-5381.2012.01873.x","article-title":"Preclinical Studies Identify Novel Targeted Pharmacological Strategies for Treatment of Human Malignant Pleural Mesothelioma","volume":"166","author":"Favoni","year":"2012","journal-title":"Br. J. Pharm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1200\/JCO.2011.41.5869","article-title":"Multicenter, Double-Blind, Placebo-Controlled, Randomized Phase II Trial of Gemcitabine\/Cisplatin Plus Bevacizumab or Placebo in Patients With Malignant Mesothelioma","volume":"30","author":"Kindler","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1038\/bjc.2013.368","article-title":"Phase II Study of Pemetrexed and Carboplatin plus Bevacizumab as First-Line Therapy in Malignant Pleural Mesothelioma","volume":"109","author":"Ceresoli","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1016\/S0140-6736(15)01238-6","article-title":"Bevacizumab for Newly Diagnosed Pleural Mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): A Randomised, Controlled, Open-Label, Phase 3 Trial","volume":"387","author":"Zalcman","year":"2016","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4340","DOI":"10.1158\/0008-5472.CAN-07-6705","article-title":"Vascular Endothelial Growth Factor Receptor 2 Mediates Macrophage Infiltration into Orthotopic Pancreatic Tumors in Mice","volume":"68","author":"Dineen","year":"2008","journal-title":"Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.pharmthera.2016.06.001","article-title":"Antagonist Antibodies to Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) as Anti-Angiogenic Agents","volume":"164","author":"Falcon","year":"2016","journal-title":"Pharmacol. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1016\/S1470-2045(21)00404-6","article-title":"Gemcitabine with or without Ramucirumab as Second-Line Treatment for Malignant Pleural Mesothelioma (RAMES): A Randomised, Double-Blind, Placebo-Controlled, Phase 2 Trial","volume":"22","author":"Pinto","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.cytogfr.2004.03.007","article-title":"The PDGF Family: Four Gene Products Form Five Dimeric Isoforms","volume":"15","author":"Fredriksson","year":"2004","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.mam.2017.11.007","article-title":"The PDGF\/PDGFR Pathway as a Drug Target","volume":"62","author":"Papadopoulos","year":"2018","journal-title":"Mol. Asp. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"a009100","DOI":"10.1101\/cshperspect.a009100","article-title":"Structural and Functional Properties of Platelet-Derived Growth Factor and Stem Cell Factor Receptors","volume":"5","author":"Heldin","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_30","first-page":"2005","article-title":"Human Malignant Mesothelioma Cell Lines Express PDGF Beta-Receptors Whereas Cultured Normal Mesothelial Cells Express Predominantly PDGF Alpha-Receptors","volume":"6","author":"Versnel","year":"1991","journal-title":"Oncogene"},{"key":"ref_31","first-page":"437","article-title":"Modulation of Platelet-Derived Growth Factor-Beta MRNA Expression and Cell Growth in a Human Mesothelioma Cell Line by a Hammerhead Ribozyme","volume":"46","author":"Dorai","year":"1994","journal-title":"Mol. Pharm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"438","DOI":"10.18632\/genesandcancer.129","article-title":"Inhibition of the Platelet-Derived Growth Factor Receptor Beta (PDGFRB) Using Gene Silencing, Crenolanib Besylate, or Imatinib Mesylate Hampers the Malignant Phenotype of Mesothelioma Cell Lines","volume":"8","author":"Melaiu","year":"2017","journal-title":"Genes Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1159\/000087376","article-title":"Serum PDGF-AB in Pleural Mesothelioma","volume":"26","author":"Filiberti","year":"2005","journal-title":"Tumor Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1136\/thx.2006.069872","article-title":"Preliminary Data Suggestive of a Novel Translational Approach to Mesothelioma Treatment: Imatinib Mesylate with Gemcitabine or Pemetrexed","volume":"62","author":"Bertino","year":"2007","journal-title":"Thorax"},{"key":"ref_35","first-page":"5476","article-title":"Inhibition of PDGF Receptor Signaling in Tumor Stroma Enhances Antitumor Effect of Chemotherapy","volume":"62","author":"Pietras","year":"2002","journal-title":"Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7200","DOI":"10.1200\/jco.2004.22.90140.7200","article-title":"A Phase II Trial of Imatinib Mesylate in Patients (Pts) with Malignant Mesothelioma (MM)","volume":"22","author":"Villano","year":"2004","journal-title":"J. Clin. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.lungcan.2005.04.010","article-title":"van Limited Efficacy of Imatinib Mesylate in Malignant Mesothelioma: A Phase II Trial","volume":"50","author":"Mathy","year":"2005","journal-title":"Lung Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1158\/1078-0432.CCR-07-1388","article-title":"Imatinib Mesylate Enhances Therapeutic Effects of Gemcitabine in Human Malignant Mesothelioma Xenografts","volume":"14","author":"Bertino","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.ejca.2005.12.010","article-title":"Selective Kinase Inhibition with Daily Imatinib Intensifies Toxicity of Chemotherapy in Patients with Solid Tumours","volume":"42","author":"George","year":"2006","journal-title":"Eur. J. Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5876","DOI":"10.1158\/1078-0432.CCR-07-0883","article-title":"Phase I and Pharmacokinetic Study of Imatinib Mesylate (Gleevec) and Gemcitabine in Patients with Refractory Solid Tumors","volume":"13","author":"Ali","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.lungcan.2020.02.005","article-title":"A Phase II Study of the Combination of Gemcitabine and Imatinib Mesylate in Pemetrexed-Pretreated Patients with Malignant Pleural Mesothelioma","volume":"142","author":"Zucali","year":"2020","journal-title":"Lung Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.cllc.2013.12.008","article-title":"Phase I Trial of Cisplatin, Pemetrexed, and Imatinib Mesylate in Chemonaive Patients With Unresectable Malignant Pleural Mesothelioma","volume":"15","author":"Tsao","year":"2014","journal-title":"Clin. Lung Cancer"},{"key":"ref_43","first-page":"5242","article-title":"Inhibition of Epidermal Growth Factor Receptor Signaling in Malignant Pleural Mesothelioma","volume":"62","author":"Taffaro","year":"2002","journal-title":"Cancer Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1056\/NEJMra0707704","article-title":"EGFR Antagonists in Cancer Treatment","volume":"358","author":"Ciardiello","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1038\/bjc.1994.410","article-title":"Autocrine Stimulation of a Human Lung Mesothelioma Cell Line Is Mediated through the Transforming Growth Factor Alpha\/Epidermal Growth Factor Receptor Mitogenic Pathway","volume":"70","author":"Schmitter","year":"1994","journal-title":"Br. J. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1038\/bjc.2011.400","article-title":"Preclinical Emergence of Vandetanib as a Potent Antitumour Agent in Mesothelioma: Molecular Mechanisms Underlying Its Synergistic Interaction with Pemetrexed and Carboplatin","volume":"105","author":"Giovannetti","year":"2011","journal-title":"Br. J. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1016\/j.jtcvs.2004.10.040","article-title":"The Selective Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor PD153035 Suppresses Expression of Prometastasis Phenotypes in Malignant Pleural Mesothelioma Cells in Vitro","volume":"129","author":"Cole","year":"2005","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2300","DOI":"10.1158\/1078-0432.CCR-04-1940","article-title":"Gefitinib in Patients with Malignant Mesothelioma: A Phase II Study by the Cancer and Leukemia Group B","volume":"11","author":"Govindan","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1200\/JCO.2006.09.7634","article-title":"Phase II Study of Erlotinib in Patients With Malignant Pleural Mesothelioma: A Southwest Oncology Group Study","volume":"25","author":"Garland","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1111\/j.1349-7006.2007.00510.x","article-title":"Antibody-Dependent Cellular Cytotoxicity of Cetuximab against Tumor Cells with Wild-Type or Mutant Epidermal Growth Factor Receptor","volume":"98","author":"Kimura","year":"2007","journal-title":"Cancer Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.3892\/ijo.2012.1607","article-title":"Therapeutic Antitumor Efficacy of Anti-Epidermal Growth Factor Receptor Antibody, Cetuximab, against Malignant Pleural Mesothelioma","volume":"41","author":"Kurai","year":"2012","journal-title":"Int. J. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e20030","DOI":"10.1200\/JCO.2017.35.15_suppl.e20030","article-title":"Cetuximab plus Platinum-Based Chemotherapy in Patients with Malignant Pleural Mesothelioma: A Single Arm Phase II Trial","volume":"35","author":"Vermaelen","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.phrs.2016.03.024","article-title":"Blocking the FGF\/FGFR System as a \u201cTwo-Compartment\u201d Antiangiogenic\/Antitumor Approach in Cancer Therapy","volume":"107","author":"Giacomini","year":"2016","journal-title":"Pharm. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/wdev.176","article-title":"The Fibroblast Growth Factor Signaling Pathway","volume":"4","author":"Ornitz","year":"2015","journal-title":"WIREs Dev. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Szymczyk, J., Sluzalska, K.D., Materla, I., Opalinski, L., Otlewski, J., and Zakrzewska, M. (2021). FGF\/FGFR-Dependent Molecular Mechanisms Underlying Anti-Cancer Drug Resistance. Cancers, 13.","DOI":"10.3390\/cancers13225796"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1164\/rccm.201404-0658OC","article-title":"Fibroblast Growth Factor Receptor Inhibition Is Active against Mesothelioma and Synergizes with Radio- and Chemotherapy","volume":"190","author":"Schelch","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1093\/carcin\/bgy018","article-title":"FGF2 and EGF Induce Epithelial\u2013Mesenchymal Transition in Malignant Pleural Mesothelioma Cells via a MAPKinase\/MMP1 Signal","volume":"39","author":"Schelch","year":"2018","journal-title":"Carcinogenesis"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/s10637-019-00783-7","article-title":"A Phase Ib Study of GSK3052230, an FGF Ligand Trap in Combination with Pemetrexed and Cisplatin in Patients with Malignant Pleural Mesothelioma","volume":"38","author":"Levchenko","year":"2020","journal-title":"Investig. New Drugs"},{"key":"ref_59","unstructured":"(2023, May 02). Available online: Https:\/\/Clinicaltrials.Gov\/."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"103234","DOI":"10.1016\/j.critrevonc.2021.103234","article-title":"Combination of HGF\/MET-Targeting Agents and Other Therapeutic Strategies in Cancer","volume":"160","author":"Moosavi","year":"2021","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"327","DOI":"10.3390\/biomedicines2040327","article-title":"HGF\/Met Signaling Is a Key Player in Malignant Mesothelioma Carcinogenesis","volume":"2","author":"Gaudino","year":"2014","journal-title":"Biomedicines"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/s004320050171","article-title":"Hepatocyte Growth Factor\/Scatter Factor and Its Receptor c-Met Are Overexpressed and Associated with an Increased Microvessel Density in Malignant Pleural Mesothelioma","volume":"124","author":"Tolnay","year":"1998","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3087","DOI":"10.1158\/0008-5472.CAN-12-3256","article-title":"Cytotoxic Activity of Tivantinib (ARQ 197) Is Not Due Solely to c-MET Inhibition","volume":"73","author":"Katayama","year":"2013","journal-title":"Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1093\/annonc\/mdu127","article-title":"Expression Profiling Stratifies Mesothelioma Tumors and Signifies Deregulation of Spindle Checkpoint Pathway and Microtubule Network with Therapeutic Implications","volume":"25","author":"Suraokar","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.2174\/1389450116666141205160924","article-title":"Synergistic Activity of the C-Met and Tubulin Inhibitor Tivantinib (ARQ197) with Pemetrexed in Mesothelioma Cells","volume":"15","author":"Leon","year":"2014","journal-title":"Curr. Drug. Targets"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.1200\/jco.2015.33.15_suppl.2549","article-title":"Phase I Trial of Tivantinib in Combination with Carboplatin and Pemetrexed as First-Line Treatment in Patients with Advanced Nonsquamous Non Small Cell Lung Cancer or Malignant Pleural Mesothelioma","volume":"33","author":"Zucali","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"7511","DOI":"10.1200\/jco.2015.33.15_suppl.7511","article-title":"ARQ 197 in Patients with Previously-Treated Malignant Mesothelioma (MM): A Phase II Trial from the University of Chicago Phase II Consortium","volume":"33","author":"Maron","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.lungcan.2011.11.014","article-title":"Vatalanib in Malignant Mesothelioma: A Phase II Trial by the Cancer and Leukemia Group B (CALGB 30107)","volume":"76","author":"Jahan","year":"2012","journal-title":"Lung Cancer"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1097\/JTO.0b013e318248242c","article-title":"Phase II Study of Dasatinib in Patients with Previously Treated Malignant Mesothelioma (Cancer and Leukemia Group B 30601): A Brief Report","volume":"7","author":"Dudek","year":"2012","journal-title":"J. Thorac. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1097\/JTO.0b013e31825f22ee","article-title":"A Phase II Study of Intermittent Sunitinib Malate as Second-Line Therapy in Progressive Malignant Pleural Mesothelioma","volume":"7","author":"Nowak","year":"2012","journal-title":"J. Thorac. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1097\/JTO.0b013e3182333df5","article-title":"Brief Report: A Phase II Study of Sunitinib in Malignant Pleural Mesothelioma. The NCIC Clinical Trials Group","volume":"6","author":"Laurie","year":"2011","journal-title":"J. Thorac. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1097\/JTO.0b013e31828c2b26","article-title":"Phase 2 Study of Sorafenib in Malignant Mesothelioma Previously Treated with Platinum-Containing Chemotherapy","volume":"8","author":"Papa","year":"2013","journal-title":"J. Thorac. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1097\/JTO.0b013e318229586e","article-title":"Phase II Study of Cediranib in Patients with Malignant Pleural Mesothelioma: SWOG S0509","volume":"6","author":"Garland","year":"2011","journal-title":"J. Thorac. Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1200\/JCO.19.00269","article-title":"Phase II Trial of Cediranib in Combination With Cisplatin and Pemetrexed in Chemotherapy-Na\u00efve Patients With Unresectable Malignant Pleural Mesothelioma (SWOG S0905)","volume":"37","author":"Tsao","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3729","DOI":"10.1158\/1078-0432.CCR-17-1507","article-title":"Nintedanib Is Active in Malignant Pleural Mesothelioma Cell Models and Inhibits Angiogenesis and Tumor Growth In Vivo","volume":"24","author":"Laszlo","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3591","DOI":"10.1200\/JCO.2017.72.9012","article-title":"Nintedanib Plus Pemetrexed\/Cisplatin in Patients With Malignant Pleural Mesothelioma: Phase II Results From the Randomized, Placebo-Controlled LUME-Meso Trial","volume":"35","author":"Grosso","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/S2213-2600(19)30139-0","article-title":"Nintedanib in Combination with Pemetrexed and Cisplatin for Chemotherapy-Naive Patients with Advanced Malignant Pleural Mesothelioma (LUME-Meso): A Double-Blind, Randomised, Placebo-Controlled Phase 3 Trial","volume":"7","author":"Scagliotti","year":"2019","journal-title":"Lancet Respir. Med."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Ocana, A., Vera-Badillo, F., Al-Mubarak, M., Templeton, A.J., Corrales-Sanchez, V., Diez-Gonzalez, L., Cuenca-Lopez, M.D., Seruga, B., Pandiella, A., and Amir, E. (2014). Activation of the PI3K\/MTOR\/AKT Pathway and Survival in Solid Tumors: Systematic Review and Meta-Analysis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095219"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1177\/0960327114542965","article-title":"EF24 and RAD001 Potentiates the Anticancer Effect of Platinum-Based Agents in Human Malignant Pleural Mesothelioma (MSTO-211H) Cells and Protects Nonmalignant Mesothelial (MET-5A) Cells","volume":"34","author":"Onen","year":"2015","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1097\/JTO.0000000000000360","article-title":"SWOG S0722: Phase II Study of MTOR Inhibitor Everolimus (RAD001) in Advanced Malignant Pleural Mesothelioma (MPM)","volume":"10","author":"Ou","year":"2015","journal-title":"J. Thorac. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1038\/bjc.2014.220","article-title":"Multipoint Targeting of the PI3K\/MTOR Pathway in Mesothelioma","volume":"110","author":"Zhou","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1007\/s10637-021-01086-6","article-title":"Phase 1 Cohort Expansion Study of LY3023414, a Dual PI3K\/MTOR Inhibitor, in Patients with Advanced Mesothelioma","volume":"39","author":"Zauderer","year":"2021","journal-title":"Investig. New Drugs"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0165-4608(89)90105-2","article-title":"Specificity of Asbestos-Induced Chromosomal Aberrations in Short-Term Cultured Human Mesothelial Cells","volume":"41","author":"Olofsson","year":"1989","journal-title":"Cancer Genet. Cytogenet."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.critrevonc.2016.08.011","article-title":"The Resistance Related to Targeted Therapy in Malignant Pleural Mesothelioma: Why Has Not the Target Been Hit Yet?","volume":"107","author":"Bronte","year":"2016","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s11864-011-0153-5","article-title":"Gene Therapy for Mesothelioma","volume":"12","author":"Vachani","year":"2011","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3810","DOI":"10.1038\/sj.onc.1202737","article-title":"Tissue-Specific Alternative Splicing in the Human INK4a\/ARF Cell Cycle Regulatory Locus","volume":"18","author":"Robertson","year":"1999","journal-title":"Oncogene"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/S1470-2045(22)00062-6","article-title":"Abemaciclib in Patients with P16ink4A-Deficient Mesothelioma (MiST2): A Single-Arm, Open-Label, Phase 2 Trial","volume":"23","author":"Fennell","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4485","DOI":"10.1158\/1078-0432.CCR-11-2375","article-title":"New Strategies in Pleural Mesothelioma: BAP1 and NF2 as Novel Targets for Therapeutic Development and Risk Assessment","volume":"18","author":"Ladanyi","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1080\/15384047.2017.1416937","article-title":"Focal Adhesion Kinase a Potential Therapeutic Target for Pancreatic Cancer and Malignant Pleural Mesothelioma","volume":"19","author":"Kanteti","year":"2018","journal-title":"Cancer Biol. Ther."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1093\/annonc\/mdw427","article-title":"A Phase I, Pharmacokinetic and Pharmacodynamic Study of GSK2256098, a Focal Adhesion Kinase Inhibitor, in Patients with Advanced Solid Tumors","volume":"27","author":"Soria","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/s41416-019-0452-3","article-title":"A Phase Ib Dose-Finding, Pharmacokinetic Study of the Focal Adhesion Kinase Inhibitor GSK2256098 and Trametinib in Patients with Advanced Solid Tumours","volume":"120","author":"Mak","year":"2019","journal-title":"Br. J. Cancer"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1200\/JCO.2018.79.0543","article-title":"Maintenance Defactinib Versus Placebo After First-Line Chemotherapy in Patients With Merlin-Stratified Pleural Mesothelioma: COMMAND\u2014A Double-Blind, Randomized, Phase II Study","volume":"37","author":"Fennell","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1158\/0008-5472.CAN-20-3430","article-title":"Roles of the BAP1 Tumor Suppressor in Cell Metabolism","volume":"81","author":"Han","year":"2021","journal-title":"Cancer Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/S2213-2600(20)30390-8","article-title":"Rucaparib in Patients with BAP1-Deficient or BRCA1-Deficient Mesothelioma (MiST1): An Open-Label, Single-Arm, Phase 2a Clinical Trial","volume":"9","author":"Fennell","year":"2021","journal-title":"Lancet Respir. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1007\/s00280-017-3401-y","article-title":"Synthetic Lethality in Malignant Pleural Mesothelioma with PARP1 Inhibition","volume":"80","author":"Srinivasan","year":"2017","journal-title":"Cancer Chemother. Pharm."},{"key":"ref_96","first-page":"100231","article-title":"Phase 2 Study of Olaparib in Malignant Mesothelioma and Correlation of Efficacy With Germline or Somatic Mutations in BAP1 Gene","volume":"2","author":"Ghafoor","year":"2021","journal-title":"JTO Clin. Res. Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3122","DOI":"10.1200\/JCO.2022.40.16_suppl.3122","article-title":"Results of a Phase II Trial of the PARP Inhibitor, Niraparib, in BAP1 and Other DNA Damage Response Pathway Deficient Neoplasms","volume":"40","author":"George","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e63","DOI":"10.1016\/j.cllc.2020.07.014","article-title":"A Prospective Phase II Single-Arm Study of Niraparib Plus Dostarlimab in Patients With Advanced Non\u2013Small-Cell Lung Cancer and\/or Malignant Pleural Mesothelioma, Positive for PD-L1 Expression and Germline or Somatic Mutations in the DNA Repair Genes: Rationale and Study Design","volume":"22","author":"Passiglia","year":"2021","journal-title":"Clin. Lung Cancer"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1002\/ijc.20372","article-title":"Histone Deacetylase Inhibitors: Understanding a New Wave of Anticancer Agents","volume":"112","author":"Esteller","year":"2004","journal-title":"Int. J. Cancer"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1097\/JTO.0b013e3181c5e366","article-title":"Histone Deacetylase Inhibitors in Malignant Pleural Mesothelioma: Preclinical Rationale and Clinical Trials","volume":"5","author":"Paik","year":"2010","journal-title":"J. Thorac. Oncol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/S1470-2045(15)70056-2","article-title":"Vorinostat in Patients with Advanced Malignant Pleural Mesothelioma Who Have Progressed on Previous Chemotherapy (VANTAGE-014): A Phase 3, Double-Blind, Randomised, Placebo-Controlled Trial","volume":"16","author":"Krug","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1097\/JTO.0b013e318191520c","article-title":"Phase II Study of Belinostat (PXD101), a Histone Deacetylase Inhibitor, for Second Line Therapy of Advanced Malignant Pleural Mesothelioma","volume":"4","author":"Ramalingam","year":"2009","journal-title":"J. Thorac. Oncol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13072-020-00369-1","article-title":"Post-Translational Modifications of PRC2: Signals Directing Its Activity","volume":"13","author":"Yang","year":"2020","journal-title":"Epigenet. Chromatin"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1038\/nm.3947","article-title":"Loss of BAP1 Function Leads to EZH2-Dependent Transformation","volume":"21","author":"LaFave","year":"2015","journal-title":"Nat. Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/S1470-2045(22)00277-7","article-title":"EZH2 Inhibitor Tazemetostat in Patients with Relapsed or Refractory, BAP1-Inactivated Malignant Pleural Mesothelioma: A Multicentre, Open-Label, Phase 2 Study","volume":"23","author":"Zauderer","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1097\/01.pai.00000141545.36485.d6","article-title":"Localization of Mesothelin in Epithelial Ovarian Cancer","volume":"13","author":"Hassan","year":"2005","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_107","first-page":"3862","article-title":"Mesothelin Is Overexpressed in the Vast Majority of Ductal Adenocarcinomas of the Pancreas: Identification of a New Pancreatic Cancer Marker by Serial Analysis of Gene Expression (SAGE)","volume":"7","author":"Argani","year":"2001","journal-title":"Clin. Cancer Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.1158\/1078-0432.CCR-11-2614","article-title":"Mesothelin Overexpression Promotes Mesothelioma Cell Invasion and MMP-9 Secretion in an Orthotopic Mouse Model and in Epithelioid Pleural Mesothelioma Patients","volume":"18","author":"Servais","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"5144","DOI":"10.1158\/1078-0432.CCR-07-0869","article-title":"Phase I Study of SS1P, a Recombinant Anti-Mesothelin Immunotoxin Given as a Bolus I.V. Infusion to Patients with Mesothelin-Expressing Mesothelioma, Ovarian, and Pancreatic Cancers","volume":"13","author":"Hassan","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"5274","DOI":"10.1158\/1078-0432.CCR-09-0062","article-title":"Phase I Trial of Continuous Infusion Anti-Mesothelin Recombinant Immunotoxin SS1P","volume":"15","author":"Kreitman","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3311","DOI":"10.1002\/cncr.28875","article-title":"Phase 1 Study of the Antimesothelin Immunotoxin SS1P in Combination with Pemetrexed and Cisplatin for Front-Line Therapy of Pleural Mesothelioma and Correlation of Tumor Response with Serum Mesothelin, Megakaryocyte Potentiating Factor, and Cancer Antigen","volume":"120","author":"Hassan","year":"2014","journal-title":"Cancer"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.1158\/1078-0432.CCR-11-0493","article-title":"Pentostatin Plus Cyclophosphamide Safely and Effectively Prevents Immunotoxin Immunogenicity in Murine Hosts","volume":"17","author":"Mossoba","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"208ra147","DOI":"10.1126\/scitranslmed.3006941","article-title":"Major Cancer Regressions in Mesothelioma After Treatment with an Anti-Mesothelin Immunotoxin and Immune Suppression","volume":"5","author":"Hassan","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"4936","DOI":"10.1002\/cncr.33145","article-title":"Phase 1 Study of the Immunotoxin LMB-100 in Patients with Mesothelioma and Other Solid Tumors Expressing Mesothelin","volume":"126","author":"Hassan","year":"2020","journal-title":"Cancer"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1158\/1078-0432.CCR-16-1667","article-title":"Efficacy of Anti-Mesothelin Immunotoxin RG7787 plus Nab-Paclitaxel against Mesothelioma Patient\u2013Derived Xenografts and Mesothelin as a Biomarker of Tumor Response","volume":"23","author":"Zhang","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1158\/2326-6066.CIR-16-0330","article-title":"Combining Local Immunotoxins Targeting Mesothelin with CTLA-4 Blockade Synergistically Eradicates Murine Cancer by Promoting Anticancer Immunity","volume":"5","author":"Leshem","year":"2017","journal-title":"Cancer Immunol. Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"6132","DOI":"10.1158\/1078-0432.CCR-10-2275","article-title":"Phase I Clinical Trial of the Chimeric Anti-Mesothelin Monoclonal Antibody MORAb-009 in Patients with Mesothelin-Expressing Cancers","volume":"16","author":"Hassan","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"5927","DOI":"10.1158\/1078-0432.CCR-14-0804","article-title":"Phase II Clinical Trial of Amatuximab, a Chimeric Antimesothelin Antibody with Pemetrexed and Cisplatin in Advanced Unresectable Pleural Mesothelioma","volume":"20","author":"Hassan","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1158\/1535-7163.MCT-13-0926","article-title":"Anetumab Ravtansine: A Novel Mesothelin-Targeting Antibody\u2013Drug Conjugate Cures Tumors with Heterogeneous Target Expression Favored by Bystander Effect","volume":"13","author":"Golfier","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1200\/JCO.19.02085","article-title":"First-in-Human, Multicenter, Phase I Dose-Escalation and Expansion Study of Anti-Mesothelin Antibody\u2013Drug Conjugate Anetumab Ravtansine in Advanced or Metastatic Solid Tumors","volume":"38","author":"Hassan","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"A095","DOI":"10.1158\/1535-7163.TARG-17-A095","article-title":"Abstract A095: Phase Ib Study of Anetumab Ravtansine in Combination with Pemetrexed and Cisplatin in Patients with Mesothelin-Expressing Epithelial Mesothelioma or Nonsquamous Non-Small Cell Lung Cancer","volume":"17","author":"Hassan","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/S1470-2045(22)00061-4","article-title":"Anetumab Ravtansine versus Vinorelbine in Patients with Relapsed, Mesothelin-Positive Malignant Pleural Mesothelioma (ARCS-M): A Randomised, Open-Label Phase 2 Trial","volume":"23","author":"Kindler","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Yeo, D., Castelletti, L., van Zandwijk, N., and Rasko, J.E.J. (2021). Hitting the Bull\u2019s-Eye: Mesothelin\u2019s Role as a Biomarker and Therapeutic Target for Malignant Pleural Mesothelioma. Cancers, 13.","DOI":"10.3390\/cancers13163932"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"7126","DOI":"10.1158\/1078-0432.CCR-06-1101","article-title":"In Vivo Loss of Expression of Argininosuccinate Synthetase in Malignant Pleural Mesothelioma Is a Biomarker for Susceptibility to Arginine Depletion","volume":"12","author":"Szlosarek","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"251","DOI":"10.4143\/crt.2013.45.4.251","article-title":"Targeting Arginine-Dependent Cancers with Arginine-Degrading Enzymes: Opportunities and Challenges","volume":"45","author":"Phillips","year":"2013","journal-title":"Cancer Res. Treat."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1001\/jamaoncol.2016.3049","article-title":"Arginine Deprivation With Pegylated Arginine Deiminase in Patients With Argininosuccinate Synthetase 1\u2013Deficient Malignant Pleural Mesothelioma","volume":"3","author":"Szlosarek","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1200\/JCO.2016.71.3230","article-title":"Phase 1 Dose-Escalation Study of Pegylated Arginine Deiminase, Cisplatin, and Pemetrexed in Patients With Argininosuccinate Synthetase 1\u2013Deficient Thoracic Cancers","volume":"35","author":"Beddowes","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_128","first-page":"100093","article-title":"Expansion Phase 1 Study of Pegargiminase Plus Pemetrexed and Cisplatin in Patients With Argininosuccinate Synthetase 1\u2013Deficient Mesothelioma: Safety, Efficacy, and Resistance Mechanisms","volume":"1","author":"Szlosarek","year":"2020","journal-title":"JTO Clin. Res. Rep."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/nri2303","article-title":"Immunobiology of the TAM Receptors","volume":"8","author":"Lemke","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1007\/s00018-011-0863-7","article-title":"Macrophage\u2013Tumor Crosstalk: Role of TAMR Tyrosine Kinase Receptors and of Their Ligands","volume":"69","author":"Schmidt","year":"2012","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"3442","DOI":"10.1038\/onc.2009.212","article-title":"Axl as a Potential Therapeutic Target in Cancer: Role of Axl in Tumor Growth, Metastasis and Angiogenesis","volume":"28","author":"Li","year":"2009","journal-title":"Oncogene"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1158\/1078-0432.CCR-0607-3","article-title":"Gene Expression Profiles Predict Survival and Progression of Pleural Mesothelioma","volume":"10","author":"Pass","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Song, W., Wang, H., Lu, M., Ni, X., Bahri, N., Zhu, S., Chen, L., Wu, Y., Qiu, J., and Fletcher, J.A. (2020). AXL Inactivation Inhibits Mesothelioma Growth and Migration via Regulation of P53 Expression. Cancers, 12.","DOI":"10.3390\/cancers12102757"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"970","DOI":"10.3389\/fphar.2017.00970","article-title":"Cisplatin and Pemetrexed Activate AXL and AXL Inhibitor BGB324 Enhances Mesothelioma Cell Death from Chemotherapy","volume":"8","author":"Oien","year":"2018","journal-title":"Front. Pharm."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.tibs.2015.12.001","article-title":"The Warburg Effect: How Does It Benefit Cancer Cells?","volume":"41","author":"Liberti","year":"2016","journal-title":"Trends Biochem. Sci."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1042\/BST20160094","article-title":"The Warburg Effect: 80 Years On","volume":"44","author":"Potter","year":"2016","journal-title":"Biochem. Soc. Trans."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"e5706","DOI":"10.1097\/MD.0000000000005706","article-title":"Pretreatment Elevated Serum Lactate Dehydrogenase as a Significant Prognostic Factor in Malignant Mesothelioma","volume":"95","author":"Zhuo","year":"2016","journal-title":"Medicine"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.semcancer.2022.09.001","article-title":"Lactate Dehydrogenase and Its Clinical Significance in Pancreatic and Thoracic Cancers","volume":"86","author":"Comandatore","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.ejps.2012.08.012","article-title":"Galloflavin, a New Lactate Dehydrogenase Inhibitor, Induces the Death of Human Breast Cancer Cells with Different Glycolytic Attitude by Affecting Distinct Signaling Pathways","volume":"47","author":"Farabegoli","year":"2012","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1038\/nchembio.2143","article-title":"Metabolic Plasticity Underpins Innate and Acquired Resistance to LDHA Inhibition","volume":"12","author":"Boudreau","year":"2016","journal-title":"Nat. Chem. Biol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"11886","DOI":"10.18632\/oncotarget.2620","article-title":"Different Effects of LDH-A Inhibition by Oxamate in Non-Small Cell Lung Cancer Cells","volume":"5","author":"Yang","year":"2014","journal-title":"Oncotarget"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1080\/15257770.2016.1149193","article-title":"A Specific Inhibitor of Lactate Dehydrogenase Overcame the Resistance toward Gemcitabine in Hypoxic Mesothelioma Cells, and Modulated the Expression of the Human Equilibrative Transporter-1","volume":"35","author":"Giovannetti","year":"2016","journal-title":"Nucl. Nucl. Nucleic Acids"},{"key":"ref_143","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_144","doi-asserted-by":"crossref","unstructured":"Franczak, M.A., Krol, O., Harasim, G., Jedrzejewska, A., Zaffaroni, N., Granchi, C., Minutolo, F., Avan, A., Giovannetti, E., and Smolenski, R.T. (2023). Metabolic Effects of New Glucose Transporter (GLUT-1) and Lactate Dehydrogenase-A (LDH-A) Inhibitors against Chemoresistant Malignant Mesothelioma. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24097771"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.mam.2012.07.001","article-title":"The SLC2 (GLUT) Family of Membrane Transporters","volume":"34","author":"Mueckler","year":"2013","journal-title":"Mol. Asp. Med."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1593\/tlo.11256","article-title":"Glut-1 Expression Correlates with Basal-like Breast Cancer","volume":"4","author":"Hussein","year":"2011","journal-title":"Transl. Oncol."},{"key":"ref_147","first-page":"2423","article-title":"Inhibition of Glucose-Transporter 1 (GLUT-1) Expression Reversed Warburg Effect in Gastric Cancer Cell MKN45","volume":"8","author":"Zhang","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.gene.2018.12.006","article-title":"The Clinicopathologic Impacts and Prognostic Significance of GLUT1 Expression in Patients with Lung Cancer: A Meta-Analysis","volume":"689","author":"Zhang","year":"2019","journal-title":"Gene"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"43356","DOI":"10.18632\/oncotarget.17445","article-title":"The Prognostic Value of GLUT1 in Cancers: A Systematic Review and Meta-Analysis","volume":"8","author":"Yu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1080\/1354750X.2020.1714735","article-title":"Diagnostic Value of GLUT-1 in Distinguishing Malignant Mesothelioma from Reactive Mesothelial Cells: A Meta-Analysis","volume":"25","author":"Zhong","year":"2020","journal-title":"Biomarkers"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1007\/s00280-016-3007-9","article-title":"Inhibition of Glut1 by WZB117 Sensitizes Radioresistant Breast Cancer Cells to Irradiation","volume":"77","author":"Zhao","year":"2016","journal-title":"Cancer Chemother. Pharm."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Ma, Y., Wang, W., Idowu, M., Oh, U., Wang, X.-Y., Temkin, S., and Fang, X. (2018). Ovarian Cancer Relies on Glucose Transporter 1 to Fuel Glycolysis and Growth: Anti-Tumor Activity of BAY-876. Cancers, 11.","DOI":"10.3390\/cancers11010033"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.leukres.2015.12.008","article-title":"Inhibition of Glucose Transporter 1 Induces Apoptosis and Sensitizes Multiple Myeloma Cells to Conventional Chemotherapeutic Agents","volume":"41","author":"Matsumoto","year":"2016","journal-title":"Leuk. Res."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Stella, G.M., and Bortolotto, C. (2022). Managing Malignant Pleural Mesothelioma in the Age of Personalized Medicine: Where Are We and What Is Still Missing?. Cancers, 14.","DOI":"10.3390\/cancers14225540"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/ng.3520","article-title":"Comprehensive Genomic Analysis of Malignant Pleural Mesothelioma Identifies Recurrent Mutations, Gene Fusions and Splicing Alterations","volume":"48","author":"Bueno","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1002\/ijc.21271","article-title":"Common EGFR Mutations Conferring Sensitivity to Gefitinib in Lung Adenocarcinoma Are Not Prevalent in Human Malignant Mesothelioma","volume":"118","author":"Cortese","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1007\/s00432-008-0384-4","article-title":"Epidermal Growth Factor Receptor Gene Mutation, Amplification and Protein Expression in Malignant Pleural Mesothelioma","volume":"134","author":"Okuda","year":"2008","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1056\/NEJMoa0804385","article-title":"Mutations and Benefit from Cetuximab in Advanced Colorectal Cancer","volume":"359","author":"Karapetis","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"170","DOI":"10.3389\/fonc.2017.00170","article-title":"New Treatment Opportunities in Phosphatase and Tensin Homolog (PTEN)-Deficient Tumors: Focus on PTEN\/Focal Adhesion Kinase Pathway","volume":"7","author":"Alfieri","year":"2017","journal-title":"Front. Oncol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/11\/9165\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:40:35Z","timestamp":1760125235000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/11\/9165"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,23]]},"references-count":159,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["ijms24119165"],"URL":"https:\/\/doi.org\/10.3390\/ijms24119165","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,23]]}}}