{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:55:26Z","timestamp":1791575726752,"version":"4.3.4"},"reference-count":77,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T00:00:00Z","timestamp":1608076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Small cell lung cancer (SCLC) is an aggressive type of lung cancer with high mortality that is caused by frequent relapses and acquired resistance. Despite that several target-based approaches with potential therapeutic impact on SCLC have been identified, numerous targeted drugs have not been successful in providing improvements in cancer patients when used as single agents. A combination of targeted therapies could be a strategy to induce maximum lethal effects on cancer cells. As a starting point in the development of new drug combination strategies for the treatment of SCLC, we performed a mid-throughput screening assay by treating a panel of SCLC cell lines with BETi or AKi in combination with PARPi or EZH2i. We observed drug synergy between I-BET762 and Talazoparib, BETi and PARPi, respectively, in SCLC cells. Combinatorial efficacy was observed in MYCs-amplified and MYCs-wt SCLC cells over SCLC cells with impaired MYC signaling pathway or non-tumor cells. We indicate that drug synergy between I-BET762 and Talazoparib is associated with the attenuation HR-DSBR process and the downregulation of various players of DNA damage response by BET inhibition, such as CHEK2, PTEN, NBN, and FANCC. Our results provide a rationale for the development of new combinatorial strategies for the treatment of SCLC.<\/jats:p>","DOI":"10.3390\/ijms21249595","type":"journal-article","created":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T22:12:06Z","timestamp":1608156726000},"page":"9595","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["BET-Inhibitor I-BET762 and PARP-Inhibitor Talazoparib Synergy in Small Cell Lung Cancer Cells"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7547-2262","authenticated-orcid":false,"given":"Francesco Paolo","family":"Fiorentino","sequence":"first","affiliation":[{"name":"Department of Biomedical Science, and National Institute of Biostructures and Biosystems, University of Sassari, 07100 Sassari, Italy"},{"name":"Kitos Biotech Srls, Porto Conte Ricerche, 07041 Alghero, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Marchesi","sequence":"additional","affiliation":[{"name":"Kitos Biotech Srls, Porto Conte Ricerche, 07041 Alghero, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6177-1042","authenticated-orcid":false,"given":"Christoph","family":"Schr\u00f6der","sequence":"additional","affiliation":[{"name":"Sciomics GmbH, 69151 Neckargem\u00fcnd, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronny","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Sciomics GmbH, 69151 Neckargem\u00fcnd, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7886-4031","authenticated-orcid":false,"given":"Jun","family":"Yokota","sequence":"additional","affiliation":[{"name":"Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2815-037X","authenticated-orcid":false,"given":"Luigi","family":"Bagella","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, and National Institute of Biostructures and Biosystems, University of Sassari, 07100 Sassari, Italy"},{"name":"Center for Biotechnology, Department of Biology, Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3322\/caac.20107","article-title":"Global cancer statistics","volume":"61","author":"Jemal","year":"2011","journal-title":"CA Cancer J. 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