{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T01:37:08Z","timestamp":1789522628785,"version":"build-2803163510"},"reference-count":26,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T00:00:00Z","timestamp":1686787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["62\/20"],"award-info":[{"award-number":["62\/20"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Dacarbazine is an important drug in the therapeutic landscape of leiomyosarcoma (LMS). Alkylating agents are subjected to resistance mechanisms based on anti-apoptotic pathways and repair mechanisms, including the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). In this retrospective study, the methylation status of the MGMT promoter in histological tumor samples from patients with LMS, dacarbazine-based regimens-treated, was measured and correlated with clinical outcomes aimed at optimizing the use of dacarbazine in soft tissue sarcomas. The patients with unmethylated MGMT had better outcomes than those with methylated MGMT. Patients without MGMT methylation had better Progression Free Survival (PFS) when aged \u226562 years compared to those aged &lt;62 years, while PFS of patients with methylated MGMT was less favorable independently of age (p = 0.0054). The patients without a methylated MGMT gene had higher Disease control rate (DCR). These results are not in agreement with the role of the methylated MGMT gene in other tumors, and with this study, we demonstrated the correlation between methylated MGMT and poor prognosis; despite that, sample smallness, heterogeneity of LMS and of treatment history could be selection bias. Predictive markers of response to chemotherapies in sarcomas remain an unmet need.<\/jats:p>","DOI":"10.3390\/cells12121635","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T01:31:31Z","timestamp":1686879091000},"page":"1635","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Impact of O6-Methylguanine-DNA Methyltransferase (MGMT) Promoter Methylation on the Outcomes of Patients with Leiomyosarcoma Treated with Dacarbazine"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9993-2013","authenticated-orcid":false,"given":"Lucia","family":"Cannella","sequence":"first","affiliation":[{"name":"S.C. Sarcomi e Tumori Rari, Istituto Nazionale Tumori\u2014IRCCS\u2014Fondazione \u201cG. Pascale\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Della Monica","sequence":"additional","affiliation":[{"name":"CEINGE\u2014Biotecnologie Avanzate, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella Lucia","family":"Marretta","sequence":"additional","affiliation":[{"name":"Department of Clinical and Surgery Oncology Unit, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1682-3792","authenticated-orcid":false,"given":"Domenico","family":"Iervolino","sequence":"additional","affiliation":[{"name":"S.C. Anatomia Patologica, IsIstituto Nazionale Tumori\u2014IRCCS\u2014Fondazione \u201cG. Pascale\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Vincenzi","sequence":"additional","affiliation":[{"name":"Dipartimento di Oncologia Medica, Campus Bio-Medico University, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Rosaria","family":"De Chiara","sequence":"additional","affiliation":[{"name":"S.S.D Istopatologia dei Linfomi e dei Sarcomi, Istituto Nazionale Tumori\u2014IRCCS\u2014Fondazione \u201cG. Pascale\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0569-8570","authenticated-orcid":false,"given":"Ottavia","family":"Clemente","sequence":"additional","affiliation":[{"name":"S.C. Sarcomi e Tumori Rari, Istituto Nazionale Tumori\u2014IRCCS\u2014Fondazione \u201cG. 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Pascale\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Guida","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Tumori Rari e Melanoma, IRCCS Istituto Tumori \u201cGiovanni Paolo II\u201d, Viale O. 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