{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T14:23:43Z","timestamp":1782743023552,"version":"3.54.5"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T00:00:00Z","timestamp":1641513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Advances in the treatment of malignant pleural mesothelioma (MPM) have been disappointing, despite the apparent need for new therapeutic options for this rare and devastating cancer. Drug resistance is common and surgical intervention has brought benefits only to a subset of patients. MPM is a heterogenous disease with a surprisingly low mutation rate and recent sequencing efforts have confirmed alterations in a limited number of tumor suppressors that do not provide apparent insights into the molecular mechanisms that drive this malignancy. There is increasing evidence that epigenetic regulation leads to immune evasion and transformation in MPM. Further, the low efficacy of immune checkpoint inhibitors is consistent with a suppression of genes involved in the anti-tumor immune response. We review three promising emerging therapeutic targets (STAT3, KDM4A, heparanase) and highlight their potential effects on the immune response.<\/jats:p>","DOI":"10.3389\/fphar.2021.806570","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T05:32:37Z","timestamp":1641533557000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Novel Therapeutic Targets and Immune Dysfunction in Malignant Pleural Mesothelioma"],"prefix":"10.3389","volume":"12","author":[{"given":"Moshe","family":"Lapidot","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinivas Vinod","family":"Saladi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Salgia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Sattler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1158\/2159-8290.CD-11-0320","article-title":"Forced Mitotic Entry of S-Phase Cells as a Therapeutic Strategy Induced by Inhibition of WEE1","volume":"2","author":"Aarts","year":"2012","journal-title":"Cancer Discov."},{"key":"B2","doi-asserted-by":"publisher","first-page":"55","DOI":"10.3978\/j.issn.2218-6751.2014.07.01","article-title":"The Role of Interleukin-6 in Malignant Mesothelioma","volume":"4","author":"Abdul Rahim","year":"2015","journal-title":"Transl. Lung Cancer Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.1043\/1543-2165(2007)131[1350:EOAALS]2.0.CO;2","article-title":"Expression of Activated and Latent Signal Transducer and Activator of Transcription 3 in 303 Non-small Cell Lung Carcinomas and 44 Malignant Mesotheliomas: Possible Role for Chemotherapeutic Intervention","volume":"131","author":"Achcar","year":"2007","journal-title":"Arch. Pathol. Lab. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.ctrv.2017.08.004","article-title":"Interleukin-8 in Cancer Pathogenesis, Treatment and Follow-Up","volume":"60","author":"Alfaro","year":"2017","journal-title":"Cancer Treat. Rev."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2038","DOI":"10.3390\/cells9092038","article-title":"Nuclear Heparanase Regulates Chromatin Remodeling, Gene Expression and PTEN Tumor Suppressor Function","volume":"9","author":"Amin","year":"2020","journal-title":"Cells"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1038\/bjc.2017.356","article-title":"TAMeless Traitors: Macrophages in Cancer Progression and Metastasis","volume":"117","author":"Aras","year":"2017","journal-title":"Br. J. Cancer"},{"key":"B7","doi-asserted-by":"publisher","first-page":"753","DOI":"10.5858\/arpa.2017-0365-RA","article-title":"Malignant Mesothelioma and its Non-Asbestos Causes","volume":"142","author":"Attanoos","year":"2018","journal-title":"Arch. Pathol. Lab. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1158\/2326-6066.CIR-16-0171","article-title":"Cytotoxic T Cells in PD-L1-Positive Malignant Pleural Mesotheliomas Are Counterbalanced by Distinct Immunosuppressive Factors","volume":"4","author":"Awad","year":"2016","journal-title":"Cancer Immunol. Res."},{"key":"B9","doi-asserted-by":"publisher","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":"B10","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1093\/jnci\/djy032","article-title":"Involvement of Heparanase in the Pathogenesis of Mesothelioma: Basic Aspects and Clinical Applications","volume":"110","author":"Barash","year":"2018","journal-title":"J. Natl. Cancer Inst."},{"key":"B11","doi-asserted-by":"publisher","first-page":"777","DOI":"10.3389\/fonc.2020.00777","article-title":"Cellular Immunotherapy and Locoregional Administration of CAR T-Cells in Malignant Pleural Mesothelioma","volume":"10","author":"Belderbos","year":"2020","journal-title":"Front. Oncol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"4504","DOI":"10.1158\/0008-5472.CAN-13-2962","article-title":"Heparanase Cooperates with Ras to Drive Breast and Skin Tumorigenesis","volume":"74","author":"Boyango","year":"2014","journal-title":"Cancer Res."},{"key":"B14","doi-asserted-by":"publisher","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":"B15","doi-asserted-by":"publisher","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":"B16","doi-asserted-by":"publisher","first-page":"343","DOI":"10.3389\/fonc.2020.00343","article-title":"Emerging Treatments for Malignant Pleural Mesothelioma: Where Are We Heading?","volume":"10","author":"Cantini","year":"2020","journal-title":"Front. Oncol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1702","DOI":"10.1016\/S1470-2045(19)30532-7","article-title":"Tumour Treating Fields in Combination with Pemetrexed and Cisplatin or Carboplatin as First-Line Treatment for Unresectable Malignant Pleural Mesothelioma (STELLAR): a Multicentre, Single-Arm Phase 2 Trial","volume":"20","author":"Ceresoli","year":"2019","journal-title":"Lancet Oncol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"4544","DOI":"10.1200\/JCO.2013.49.9616","article-title":"Clinicopathologic Characteristics of Malignant Mesotheliomas Arising in Patients with a History of Radiation for Hodgkin and Non-Hodgkin Lymphoma","volume":"31","author":"Chirieac","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1097\/CCO.0000000000000053","article-title":"Systemic Treatment of Malignant Pleural Mesothelioma: New Agents in Clinical Trials Raise hope of Relevant Improvements","volume":"26","author":"Christoph","year":"2014","journal-title":"Curr. Opin. Oncol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.3389\/fonc.2019.01366","article-title":"The Immune Microenvironment in Mesothelioma: Mechanisms of Resistance to Immunotherapy","volume":"9","author":"Chu","year":"2019","journal-title":"Front. Oncol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/s41379-019-0328-3","article-title":"Expression of V-Set Immunoregulatory Receptor in Malignant Mesothelioma","volume":"33","author":"Chung","year":"2020","journal-title":"Mod. Pathol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"3526","DOI":"10.1016\/j.molcel.2021.06.020","article-title":"BAP1 Enhances Polycomb Repression by Counteracting Widespread H2AK119ub1 Deposition and Chromatin Condensation","volume":"81","author":"Conway","year":"2021","journal-title":"Mol. Cel."},{"key":"B23","doi-asserted-by":"publisher","first-page":"638279","DOI":"10.3389\/fphar.2021.638279","article-title":"Is There Already a Need of Reckoning on Cancer Immunotherapy?","volume":"12","author":"Correale","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B24","article-title":"Pathology of Mesothelioma","volume-title":"Comprehensive Textbook of Thoracic Oncology","author":"Corson","year":"1996"},{"key":"B25","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1002\/(SICI)1096-9896(199910)189:2<251:AID-PATH412>3.0.CO;2-F","article-title":"The Use of Histological and Immunohistochemical Markers to Distinguish Pleural Malignant Mesothelioma and In Situ Mesothelioma from Reactive Mesothelial Hyperplasia and Reactive Pleural Fibrosis","volume":"189","author":"Cury","year":"1999","journal-title":"J. Pathol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"5124","DOI":"10.1158\/1078-0432.CCR-14-1233","article-title":"Low PIAS3 Expression in Malignant Mesothelioma Is Associated with Increased STAT3 Activation and Poor Patient Survival","volume":"20","author":"Dabir","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1038\/s41585-018-0052-7","article-title":"Epigenetic Modifiers: Activities in Renal Cell Carcinoma","volume":"15","author":"de Cubas","year":"2018","journal-title":"Nat. Rev. Urol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1007\/s00018-015-2060-6","article-title":"The Helicase-like Transcription Factor (HLTF) in Cancer: Loss of Function or Oncomorphic Conversion of a Tumor Suppressor?","volume":"73","author":"Dhont","year":"2016","journal-title":"Cel. Mol. Life Sci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1038\/sj.emboj.7601967","article-title":"Dynamic Histone H3 Methylation during Gene Induction: HYPB\/Setd2 Mediates All H3K36 Trimethylation","volume":"27","author":"Edmunds","year":"2008","journal-title":"EMBO J."},{"key":"B30","doi-asserted-by":"publisher","first-page":"a026468","DOI":"10.1101\/cshperspect.a026468","article-title":"SETting the Stage for Cancer Development: SETD2 and the Consequences of Lost Methylation","volume":"7","author":"Fahey","year":"2017","journal-title":"Cold Spring Harb Perspect. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1002\/ijc.21046","article-title":"Dendritic Cells Delivered inside Human Carcinomas Are Sequestered by Interleukin-8","volume":"116","author":"Feijo\u00f3","year":"2005","journal-title":"Int. J. Cancer"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1530","DOI":"10.1016\/S1470-2045(21)00471-X","article-title":"Nivolumab versus Placebo in Patients with Relapsed Malignant Mesothelioma (CONFIRM): a Multicentre, Double-Blind, Randomised, Phase 3 Trial","volume":"22","author":"Fennell","year":"2021","journal-title":"Lancet Oncol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1080\/15592294.2016.1249089","article-title":"Identification and Characterization of PKF118-310 as a KDM4A Inhibitor","volume":"12","author":"Franci","year":"2017","journal-title":"Epigenetics"},{"key":"B34","doi-asserted-by":"publisher","first-page":"5445","DOI":"10.1158\/0008-5472.CAN-11-1138","article-title":"The ICOS\/ICOSL Pathway Is Required for Optimal Antitumor Responses Mediated by Anti-CTLA-4 Therapy","volume":"71","author":"Fu","year":"2011","journal-title":"Cancer Res."},{"key":"B35","first-page":"187","article-title":"Inhibition of Interleukin-8 Reduces Human Malignant Pleural Mesothelioma Propagation in Nude Mouse Model","volume":"11","author":"Galffy","year":"1999","journal-title":"Oncol. Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s11658-018-0078-0","article-title":"STAT3, Stem Cells, Cancer Stem Cells and P63","volume":"23","author":"Galoczova","year":"2018","journal-title":"Cel. Mol. Biol. Lett."},{"key":"B37","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1093\/jnci\/djp061","article-title":"Four-gene Expression Ratio Test for Survival in Patients Undergoing Surgery for Mesothelioma","volume":"101","author":"Gordon","year":"2009","journal-title":"J. Natl. Cancer Inst."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/08977194.2018.1473393","article-title":"STAT3: a Multifaceted Oncoprotein","volume":"36","author":"Guanizo","year":"2018","journal-title":"Growth Factors"},{"key":"B39","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.cancergen.2014.11.001","article-title":"The Role of the Histone Demethylase KDM4A in Cancer","volume":"208","author":"Guerra-Calderas","year":"2015","journal-title":"Cancer Genet."},{"key":"B40","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of Cancer: the Next Generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"B41","doi-asserted-by":"publisher","first-page":"278","DOI":"10.18632\/genesandcancer.120","article-title":"Dual Function of MDM2 and MDMX toward the Tumor Suppressors P53 and RB","volume":"7","author":"Hern\u00e1ndez-Monge","year":"2016","journal-title":"Genes Cancer"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1548","DOI":"10.1158\/2159-8290.CD-18-0804","article-title":"Integrative Molecular Characterization of Malignant Pleural Mesothelioma","volume":"8","author":"Hmeljak","year":"2018","journal-title":"Cancer Discov."},{"key":"B43","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1186\/s12967-020-02624-1","article-title":"Heparanase and the Hallmarks of Cancer","volume":"18","author":"Jayatilleke","year":"2020","journal-title":"J. Transl Med."},{"key":"B44","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s00262-017-2057-0","article-title":"The STAT3 Inhibitor Pyrimethamine Displays Anti-cancer and Immune Stimulatory Effects in Murine Models of Breast Cancer","volume":"67","author":"Khan","year":"2018","journal-title":"Cancer Immunol. Immunother."},{"key":"B45","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1038\/nature04853","article-title":"The Transcriptional Repressor JHDM3A Demethylates Trimethyl Histone H3 Lysine 9 and Lysine 36","volume":"442","author":"Klose","year":"2006","journal-title":"Nature"},{"key":"B46","doi-asserted-by":"publisher","first-page":"36830","DOI":"10.18632\/oncotarget.26243","article-title":"Heparanase Inhibitors Restrain Mesothelioma","volume":"9","author":"Lapidot","year":"2018","journal-title":"Oncotarget"},{"key":"B47","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3390\/cancers13010007","article-title":"Inhibitors of the Transcription Factor STAT3 Decrease Growth and Induce Immune Response Genes in Models of Malignant Pleural Mesothelioma (MPM)","volume":"13","author":"Lapidot","year":"","journal-title":"Cancers (Basel)"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000004306","article-title":"Pleurectomy Decortication in the Treatment of Malignant Pleural Mesothelioma: Encouraging Results and Novel Prognostic Implications Based on Experience in 355 Consecutive Patients","author":"Lapidot","year":"","journal-title":"Ann. Surg."},{"key":"B49","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1038\/s41416-021-01441-7","article-title":"Essential Role of the Histone Lysine Demethylase KDM4A in the Biology of Malignant Pleural Mesothelioma (MPM)","volume":"125","author":"Lapidot","year":"2021","journal-title":"Br. J. Cancer"},{"key":"B50","doi-asserted-by":"publisher","first-page":"e98575","DOI":"10.1172\/jci.insight.98575","article-title":"Comprehensive Immunoproteogenomic Analyses of Malignant Pleural Mesothelioma","volume":"3","author":"Lee","year":"2018","journal-title":"JCI Insight"},{"key":"B51","doi-asserted-by":"publisher","first-page":"99","DOI":"10.21037\/amj.2018.09.11","article-title":"Diagnosis and Management of Mesothelioma","volume":"3","author":"Liou","year":"2018","journal-title":"AME Med. J."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1016\/S1470-2045(17)30446-1","article-title":"Tremelimumab as Second-Line or Third-Line Treatment in Relapsed Malignant Mesothelioma (DETERMINE): a Multicentre, International, Randomised, Double-Blind, Placebo-Controlled Phase 2b Trial","volume":"18","author":"Maio","year":"2017","journal-title":"Lancet Oncol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1126\/science.abg5784","article-title":"The Adaptive Immune System Is a Major Driver of Selection for Tumor Suppressor Gene Inactivation","volume":"373","author":"Martin","year":"2021","journal-title":"Science"},{"key":"B54","doi-asserted-by":"publisher","first-page":"492608","DOI":"10.1155\/2012\/492608","article-title":"Asbestos-induced Cellular and Molecular Alteration of Immunocompetent Cells and Their Relationship with Chronic Inflammation and Carcinogenesis","volume":"2012","author":"Matsuzaki","year":"2012","journal-title":"J. Biomed. Biotechnol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"705","DOI":"10.3389\/fonc.2019.00705","article-title":"The Emerging Role of H3K9me3 as a Potential Therapeutic Target in Acute Myeloid Leukemia","volume":"9","author":"Monaghan","year":"2019","journal-title":"Front. Oncol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.3389\/fonc.2019.01519","article-title":"Malignant Pleural Mesothelioma: State-Of-The-Art on Current Therapies and Promises for the Future","volume":"9","author":"Nicolini","year":"2019","journal-title":"Front. Oncol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.immuni.2014.06.010","article-title":"Tumor-Associated Macrophages: from Mechanisms to Therapy","volume":"41","author":"Noy","year":"2014","journal-title":"Immunity"},{"key":"B58","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.cyto.2016.06.017","article-title":"JAK-STAT Signaling in Cancer: From Cytokines to Non-Coding Genome","volume":"87","author":"Pencik","year":"2016","journal-title":"Cytokine"},{"key":"B59","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/j.ccell.2015.09.015","article-title":"Inhibiting WEE1 Selectively Kills Histone H3K36me3-Deficient Cancers by dNTP Starvation","volume":"28","author":"Pfister","year":"2015","journal-title":"Cancer Cel."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1016\/j.annonc.2020.09.009","article-title":"A Multicentre Randomised Phase III Trial Comparing Pembrolizumab versus Single-Agent Chemotherapy for Advanced Pre-treated Malignant Pleural Mesothelioma: the European Thoracic Oncology Platform (ETOP 9-15) PROMISE-Meso Trial","volume":"31","author":"Popat","year":"2020","journal-title":"Ann. Oncol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.ctrv.2014.10.007","article-title":"Malignant Pleural Mesothelioma: new hope in the Horizon with Novel Therapeutic Strategies","volume":"41","author":"Remon","year":"2015","journal-title":"Cancer Treat. Rev."},{"key":"B62","doi-asserted-by":"publisher","first-page":"e1006839","DOI":"10.1371\/journal.ppat.1006839","article-title":"Viral Manipulation of STAT3: Evade, Exploit, and Injure","volume":"14","author":"Roca Suarez","year":"2018","journal-title":"Plos Pathog."},{"key":"B63","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.ccell.2018.07.004","article-title":"Therapeutic Ablation of Gain-Of-Function Mutant P53 in Colorectal Cancer Inhibits Stat3-Mediated Tumor Growth and Invasion","volume":"34","author":"Schulz-Heddergott","year":"2018","journal-title":"Cancer Cel."},{"key":"B64","doi-asserted-by":"publisher","first-page":"3946","DOI":"10.1158\/0008-5472.CAN-15-0037","article-title":"Heparanase Enhances Tumor Growth and Chemoresistance by Promoting Autophagy","volume":"75","author":"Shteingauz","year":"2015","journal-title":"Cancer Res."},{"key":"B65","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1177\/107327489700400404","article-title":"Current Therapy for Mesothelioma","volume":"4","author":"Sugarbaker","year":"1997","journal-title":"Cancer Control"},{"key":"B66","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/s41420-021-00406-2","article-title":"Emerging Multifaceted Roles of BAP1 Complexes in Biological Processes","volume":"7","author":"Szczepanski","year":"2021","journal-title":"Cel. Death Discov."},{"key":"B67","doi-asserted-by":"publisher","first-page":"4143","DOI":"10.1093\/hmg\/ddr338","article-title":"Pyrimethamine Inhibits Adult Polycystic Kidney Disease by Modulating STAT Signaling Pathways","volume":"20","author":"Takakura","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"B12","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/s41389-019-0159-6","article-title":"EPHA2 Mutations With Oncogenic Characteristics in Squamous Cell Lung Cancer and Malignant Pleural Mesothelioma","volume":"8","author":"Tan","year":"2019","journal-title":"Oncogenesis"},{"key":"B68","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.drup.2016.10.001","article-title":"Heparanase: From Basic Research to Therapeutic Applications in Cancer and Inflammation","volume":"29","author":"Vlodavsky","year":"2016","journal-title":"Drug Resist. Updat."},{"key":"B69","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1146\/annurev-med-041316-085813","article-title":"New Concepts in the Treatment of Malignant Pleural Mesothelioma","volume":"69","author":"Wald","year":"2018","journal-title":"Annu. Rev. Med."},{"key":"B70","doi-asserted-by":"publisher","first-page":"2035","DOI":"10.1038\/ncomms3035","article-title":"A Small Molecule Modulates Jumonji Histone Demethylase Activity and Selectively Inhibits Cancer Growth","volume":"4","author":"Wang","year":"2013","journal-title":"Nat. Commun."},{"key":"B71","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.ccr.2010.09.006","article-title":"Epigenetic Antagonism between Polycomb and SWI\/SNF Complexes during Oncogenic Transformation","volume":"18","author":"Wilson","year":"2010","journal-title":"Cancer Cell"},{"key":"B72","doi-asserted-by":"publisher","first-page":"1845","DOI":"10.1182\/blood-2015-07-660506","article-title":"Gene Expression-Based Discovery of Atovaquone as a STAT3 Inhibitor and Anticancer Agent","volume":"128","author":"Xiang","year":"2016","journal-title":"Blood"},{"key":"B73","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.3390\/cancers13071561","article-title":"NF2 and Canonical Hippo-YAP Pathway Define Distinct Tumor Subsets Characterized by Different Immune Deficiency and Treatment Implications in Human Pleural Mesothelioma","volume":"13","author":"Yang","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B74","doi-asserted-by":"publisher","first-page":"167","DOI":"10.7150\/thno.61209","article-title":"Tumor-infiltrating Lymphocytes Are Functionally Inactivated by CD90+ Stromal Cells and Reactivated by Combined Ibrutinib and Rapamycin in Human Pleural Mesothelioma","volume":"12","author":"Yang","year":"2022","journal-title":"Theranostics"},{"key":"B75","doi-asserted-by":"publisher","first-page":"13432","DOI":"10.1073\/pnas.1612074113","article-title":"High-density Array-CGH with Targeted NGS Unmask Multiple Noncontiguous Minute Deletions on Chromosome 3p21 in Mesothelioma","volume":"113","author":"Yoshikawa","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"B76","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1139\/bcb-2012-0054","article-title":"The Oncogenic Potential of Jumonji D2 (JMJD2\/KDM4) Histone Demethylase Overexpression","volume":"91","author":"Young","year":"2013","journal-title":"Biochem. Cel Biol"},{"key":"B77","doi-asserted-by":"publisher","first-page":"15701","DOI":"10.1074\/jbc.M808431200","article-title":"Heterogeneous Nuclear Ribonucleoprotein L Is a Subunit of Human KMT3a\/Set2 Complex Required for H3 Lys-36 Trimethylation Activity In Vivo","volume":"284","author":"Yuan","year":"2009","journal-title":"J. Biol. Chem."},{"key":"B78","doi-asserted-by":"publisher","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":"B79","doi-asserted-by":"publisher","first-page":"1751","DOI":"10.1038\/s41467-021-21798-w","article-title":"Clonal Architecture in Mesothelioma Is Prognostic and Shapes the Tumour Microenvironment","volume":"12","author":"Zhang","year":"2021","journal-title":"Nat. Commun."},{"key":"B80","doi-asserted-by":"publisher","first-page":"36501","DOI":"10.18632\/oncotarget.9038","article-title":"BRG1 Targeting STAT3\/VEGFC Signaling Regulates Lymphangiogenesis in Colorectal Cancer","volume":"7","author":"Zhu","year":"2016","journal-title":"Oncotarget"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.806570\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T05:32:45Z","timestamp":1641533565000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.806570\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,7]]},"references-count":80,"alternative-id":["10.3389\/fphar.2021.806570"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2021.806570","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,7]]},"article-number":"806570"}}