{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T08:40:54Z","timestamp":1762072854612,"version":"build-2065373602"},"reference-count":95,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T00:00:00Z","timestamp":1667433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01CA120528-15"],"award-info":[{"award-number":["R01CA120528-15"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pleural mesothelioma (PM) is a rare and aggressive disease that arises from the mesothelial cells lining the pleural cavity. Approximately 80% of PM patients have a history of asbestos exposure. The long latency period of 20\u201340 years from the time of asbestos exposure to diagnosis, suggests that multiple somatic genetic alterations are required for the tumorigenesis of PM. The genomic landscape of PM has been characterized by inter- and intratumor heterogeneity associated with the impairment of tumor suppressor genes such as CDKN2A, NF2, and BAP1. Current systemic therapies have shown only limited efficacy, and none is approved for patients with relapsed PM. Advances in understanding of the molecular landscape of PM has facilitated several biomarker-driven clinical trials but so far, no predictive biomarkers for targeted therapies are in clinical use. Recent advances in the PM genetics have provided optimism for successful molecular strategies in the future. Here, we summarize the molecular mechanism underlying PM pathogenesis and review potential therapeutic targets.<\/jats:p>","DOI":"10.3390\/ijms232113422","type":"journal-article","created":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T03:53:07Z","timestamp":1667447587000},"page":"13422","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Rocky Road from Preclinical Findings to Successful Targeted Therapy in Pleural Mesothelioma"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4364-2201","authenticated-orcid":false,"given":"Juuso","family":"Paajanen","sequence":"first","affiliation":[{"name":"The Thoracic Surgery Oncology Laboratory and The International Mesothelioma Program, Division of Thoracic Surgery and the Lung Center, Brigham and Women\u2019s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raphael","family":"Bueno","sequence":"additional","affiliation":[{"name":"The Thoracic Surgery Oncology Laboratory and The International Mesothelioma Program, Division of Thoracic Surgery and the Lung Center, Brigham and Women\u2019s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Assunta","family":"De Rienzo","sequence":"additional","affiliation":[{"name":"The Thoracic Surgery Oncology Laboratory and The International Mesothelioma Program, Division of Thoracic Surgery and the Lung Center, Brigham and Women\u2019s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1046\/j.1365-2559.1997.5460776.x","article-title":"Pathology of Malignant Mesothelioma","volume":"30","author":"Attanoos","year":"1997","journal-title":"Histopathology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3239","DOI":"10.1007\/s00268-019-05132-6","article-title":"Largely Unchanged Annual Incidence and Overall Survival of Pleural Mesothelioma in the USA","volume":"43","author":"Keshava","year":"2019","journal-title":"World J. 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