{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T10:34:54Z","timestamp":1787481294883,"version":"build-2736575974"},"reference-count":107,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T00:00:00Z","timestamp":1743292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ricerca corrente 5x1000-2020","award":["090000X121\u2014progetto 08050122"],"award-info":[{"award-number":["090000X121\u2014progetto 08050122"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Pleural mesothelioma (PM) is a rare and highly aggressive cancer which arises from mesothelial layer and primarily linked to asbestos exposure, genetic predispositions, and specific mutations. Despite current treatment modalities, including chemotherapy, antiangiogenic therapy and more recently immunotherapy, the prognosis remains dismal, with a median survival time of 6\u201318 months. Objectives: The urgent need for novel therapeutic strategies has prompted research into molecular targets and precision medicine approaches. At present, many potential targets for therapeutic strategies have been identified, and emerging clinical trials are demonstrating certain clinical efficacy. Methods: This review examines advancements in understanding PM\u2019s genetic and epigenetic landscape, signaling pathways, and promising therapeutic targets. Results: We also discuss the results of recent clinical trials and their potential implications for future treatment paradigms.<\/jats:p>","DOI":"10.3390\/cancers17071160","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T01:59:36Z","timestamp":1743386376000},"page":"1160","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Malignant Pleural Mesothelioma: From Pathophysiology to Innovative Actionable Targets"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7699-6610","authenticated-orcid":false,"given":"Francesco Rocco","family":"Bertuccio","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Medical Therapeutics, University of Pavia Medical School, 27100 Pavia, Italy"},{"name":"Unit of Respiratory Diseases, Cardiothoracic and Vascular Department, IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Montini","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Therapeutics, University of Pavia Medical School, 27100 Pavia, Italy"},{"name":"Unit of Respiratory Diseases, Cardiothoracic and Vascular Department, IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Antonietta","family":"Fusco","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Therapeutics, University of Pavia Medical School, 27100 Pavia, Italy"},{"name":"Unit of Respiratory Diseases, Cardiothoracic and Vascular Department, IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Di Gennaro","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Therapeutics, University of Pavia Medical School, 27100 Pavia, Italy"},{"name":"Unit of Respiratory Diseases, Cardiothoracic and Vascular Department, IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetano","family":"Sciandrone","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Therapeutics, University of Pavia Medical School, 27100 Pavia, Italy"},{"name":"Unit of Respiratory Diseases, Cardiothoracic and Vascular Department, IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4334-1230","authenticated-orcid":false,"given":"Francesco","family":"Agustoni","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Therapeutics, University of Pavia Medical School, 27100 Pavia, Italy"},{"name":"Department of Medical Oncology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Galli","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Therapeutics, University of Pavia Medical School, 27100 Pavia, Italy"},{"name":"Department of Medical Oncology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9193-9309","authenticated-orcid":false,"given":"Chandra","family":"Bortolotto","sequence":"additional","affiliation":[{"name":"Diagnostic Imaging and Radiotherapy Unit, Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Radiology Institute, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Saddi","sequence":"additional","affiliation":[{"name":"Unit of Radiation Therapy, Department of Oncology, Clinical-Surgical, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy"},{"name":"Department of Radiation Oncology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Baietto","sequence":"additional","affiliation":[{"name":"Unit of Thoracic Surgery, Cardiothoracic and Vascular Department, IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Melloni","sequence":"additional","affiliation":[{"name":"Unit of Thoracic Surgery, Cardiothoracic and Vascular Department, IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gioacchino","family":"D\u2019Ambrosio","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Diagnostical Services and Imaging, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo Guido","family":"Corsico","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Therapeutics, University of Pavia Medical School, 27100 Pavia, Italy"},{"name":"Unit of Respiratory Diseases, Cardiothoracic and Vascular Department, IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0929-4394","authenticated-orcid":false,"given":"Giulia Maria","family":"Stella","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Therapeutics, University of Pavia Medical School, 27100 Pavia, Italy"},{"name":"Unit of Respiratory Diseases, Cardiothoracic and Vascular Department, IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Abbott, D.M., Bortolotto, C., Benvenuti, S., Lancia, A., Filippi, A.R., and Stella, G.M. 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