{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T16:58:20Z","timestamp":1780419500218,"version":"3.54.1"},"reference-count":44,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T00:00:00Z","timestamp":1596758400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Advanced clear cell carcinomas originating from both ovaries and kidneys with cancerous peritonitis have poor prognoses. Murine double\u2010minute 2 (MDM2) is a potential therapeutic target for clear cell ovarian carcinomas with WT <jats:italic>TP53<\/jats:italic>. Herein, we characterized the antiangiogenic and antitumor effects of the MDM2 inhibitors DS\u20103032b and DS\u20105272 in 6 clear cell ovarian carcinoma cell lines and 2 clear cell renal carcinoma cell lines, as well as in clear cell ovarian carcinomas s.c. xenograft and ID8 (murine ovarian cancer cells with WT <jats:italic>TP53<\/jats:italic>) cancer peritonitis mouse models. In clear cell ovarian carcinoma s.c. xenograft mouse models, DS\u20103032b significantly reduced WT <jats:italic>TP53<\/jats:italic> clear cell ovarian carcinoma\u2010 and clear cell renal carcinoma\u2010derived tumor volumes. In ID8 mouse models, DS\u20105272 significantly inhibited ascites production, reduced body weight, and significantly improved overall survival. Additionally, DS\u20105272 reduced the tumor burden of peritoneal dissemination and decreased CD31<jats:sup>+<\/jats:sup> cells in a dose\u2010dependent manner. Furthermore, DS\u20105272 significantly decreased vascular endothelial growth factor concentrations in both sera and ascites. Combined therapy with MDM2 inhibitors and everolimus showed synergistic, and dose\u2010reduction potential, for clear cell carcinoma treatment. Our findings suggest that MDM2 inhibitors represent promising molecular targeted therapy for clear cell carcinomas, thereby warranting further studies to evaluate the efficacy and safety of dual MDM2\/mTOR inhibitors in clear cell carcinoma patients.<\/jats:p>","DOI":"10.1111\/cas.14583","type":"journal-article","created":{"date-parts":[[2020,7,26]],"date-time":"2020-07-26T03:19:45Z","timestamp":1595733585000},"page":"3824-3834","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effect of murine double\u2010minute 2 inhibitors in preclinical models of advanced clear cell carcinomas originating from ovaries and kidneys"],"prefix":"10.1111","volume":"111","author":[{"given":"Yoshiko","family":"Kawata","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Graduate School of Medicine The University of Tokyo Tokyo 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