{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T20:23:09Z","timestamp":1783455789110,"version":"3.55.0"},"reference-count":41,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T00:00:00Z","timestamp":1627603200000},"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>Cholangiocarcinoma is the first most common cancer of the biliary tract. To date, surgical resection is the only potentially curative option, but it is possible only for a limited percentage of patients, and in any case survival rate is quite low. Moreover, cholangiocarcinoma is often chemotherapy-resistant, and the only drug with a significant benefit for patient\u2019s survival is Gemcitabine. It is necessary to find new drugs or combination therapies to treat nonresectable cholangiocarcinoma and improve the overall survival rate of patients. In this work, we evaluate in vitro the antitumoral effects of Rigosertib, a multi-kinase inhibitor in clinical development, against cholangiocarcinoma EGI-1 cell lines. Rigosertib impairs EGI-1 cell viability in a dose- and time-dependent manner, reversibility is dose-dependent, and significant morphological and nuclear alterations occur. Moreover, Rigosertib induces the arrest of the cell cycle in the G2\/M phase, increases autophagy, and inhibits proteasome, cell migration, and invasion. Lastly, Rigosertib shows to be a stronger radiosensitizer than Gemcitabine and 5-Fluorouracil. In conclusion, Rigosertib could be a potential therapeutic option, alone or in combination with radiations, for nonresectable patients with cholangiocarcinoma.<\/jats:p>","DOI":"10.3390\/ijms22158230","type":"journal-article","created":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T12:59:24Z","timestamp":1627649964000},"page":"8230","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["In Vitro Evaluation of Rigosertib Antitumoral and Radiosensitizing Effects against Human Cholangiocarcinoma Cells"],"prefix":"10.3390","volume":"22","author":[{"given":"Alessio","family":"Malacrida","sequence":"first","affiliation":[{"name":"Experimental Neurology Unit, School of Medicine and Surgery, University of Milano\u2014Bicocca, Via Cadore 48, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Rigolio","sequence":"additional","affiliation":[{"name":"Experimental Neurology Unit, School of Medicine and Surgery, University of Milano\u2014Bicocca, Via Cadore 48, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Celio","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, ASST del Garda, 25015 Desenzano del Garda, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9560-1092","authenticated-orcid":false,"given":"Silvia","family":"Damian","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori\u2014Via Giacomo Venezian 1, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4128-2406","authenticated-orcid":false,"given":"Guido","family":"Cavaletti","sequence":"additional","affiliation":[{"name":"Experimental Neurology Unit, School of Medicine and Surgery, University of Milano\u2014Bicocca, Via Cadore 48, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Mazzaferro","sequence":"additional","affiliation":[{"name":"Department of Hepatology, Hepato Pancreatic Biliary Surgery and Liver Transplantation, Istituto Nazionale Tumori, Foundation IRCCS, 20133 Milan, Italy"},{"name":"Department of Oncology, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariarosaria","family":"Miloso","sequence":"additional","affiliation":[{"name":"Experimental Neurology Unit, School of Medicine and Surgery, University of Milano\u2014Bicocca, Via Cadore 48, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4968","DOI":"10.1158\/0008-5472.CAN-10-1603","article-title":"Effect of ON 01910.Na, an anticancer mitotic inhibitor, on cell-cycle progression correlates with RanGAP1 hyperphosphorylation","volume":"71","author":"Oussenko","year":"2011","journal-title":"Cancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1158\/1078-0432.CCR-11-2813","article-title":"Phase I study of Rigosertib, an inhibitor of the phosphatidylinositol 3-kinase and Polo-like kinase 1 pathways, combined with gemcitabine in patients with solid tumors and pancreatic cancer","volume":"18","author":"Ma","year":"2012","journal-title":"Clin. 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