{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T02:41:22Z","timestamp":1773024082166,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T00:00:00Z","timestamp":1669766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Associazione Augusto per la vita (Novellara, RE, Italy)","award":["0184\/2018"],"award-info":[{"award-number":["0184\/2018"]}]},{"name":"Transfer Oil (Colorno, PR, Italy)","award":["0184\/2018"],"award-info":[{"award-number":["0184\/2018"]}]},{"DOI":"10.13039\/100009097","name":"Fondazione Cariparma (Parma, Italy)","doi-asserted-by":"publisher","award":["0184\/2018"],"award-info":[{"award-number":["0184\/2018"]}],"id":[{"id":"10.13039\/100009097","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: The loss of the CDKN2A\/ARF (cyclin-dependent kinase inhibitor 2A\/alternative reading frame) gene is the most common alteration in malignant pleural mesothelioma (MPM), with an incidence of about 70%, thus representing a novel target for mesothelioma treatment. In the present study, we evaluated the antitumor potential of combining the standard chemotherapy regimen used for unresectable MPM with the CDK4\/6 (cyclin-dependent kinase 4 or 6) inhibitor abemaciclib. Methods: Cell viability, cell death, senescence, and autophagy induction were evaluated in two MPM cell lines and in a primary MPM cell culture. Results: The simultaneous treatment of abemaciclib with cisplatin and pemetrexed showed a greater antiproliferative effect than chemotherapy alone, both in MPM cell lines and in primary cells. This combined treatment induced cellular senescence or autophagic cell death, depending on the cell type. More in detail, the induction of cellular senescence was related to the increased expression of p21, whereas autophagy induction was due to the impairment of the AKT\/mTOR signaling. Notably, the effect of the combination was irreversible and no resumption in tumor cell proliferation was observed after drug withdrawal. Conclusion: Our results demonstrated the therapeutic potential of CDK4\/6 inhibitors in combination with chemotherapy for the treatment of MPM and are consistent with the recent positive results in the MiST2 arm in abemaciclib-treated patients.<\/jats:p>","DOI":"10.3390\/cancers14235925","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T08:46:41Z","timestamp":1669798001000},"page":"5925","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["CDK4\/6 Inhibition Enhances the Efficacy of Standard Chemotherapy Treatment in Malignant Pleural Mesothelioma Cells"],"prefix":"10.3390","volume":"14","author":[{"given":"Rita","family":"Terenziani","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8061-8649","authenticated-orcid":false,"given":"Maricla","family":"Galetti","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL-Italian Workers\u2019 Compensation Authority, Monte Porzio Catone, 00078 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3578-3917","authenticated-orcid":false,"given":"Silvia","family":"La Monica","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3291-6668","authenticated-orcid":false,"given":"Claudia","family":"Fumarola","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8357-1073","authenticated-orcid":false,"given":"Silvia","family":"Zoppi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0601-7244","authenticated-orcid":false,"given":"Roberta","family":"Alfieri","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graziana","family":"Digiacomo","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3752-1868","authenticated-orcid":false,"given":"Andrea","family":"Cavazzoni","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2331-1464","authenticated-orcid":false,"given":"Delia","family":"Cavallo","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL-Italian Workers\u2019 Compensation Authority, Monte Porzio Catone, 00078 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2808-4184","authenticated-orcid":false,"given":"Massimo","family":"Corradi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"},{"name":"Center of Excellence for Toxicological Research (CERT), University of Parma, 43126 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9553-8465","authenticated-orcid":false,"given":"Marcello","family":"Tiseo","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"},{"name":"Medical Oncology Unit, University Hospital of Parma, 43126 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pier Giorgio","family":"Petronini","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5728-7899","authenticated-orcid":false,"given":"Mara","family":"Bonelli","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 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