Novel Small Molecule MEK Inhibitor URML-3881 Enhances Cisplatin Sensitivity in Clear Cell Ovarian Cancer.

ABSTRACT: Advanced clear cell ovarian cancer (CCOC) is a highly fatal malignancy with a scarcity of effective treatment options. CCOC is inherently chemotherapy resistance, but the exact mechanism of this resistance has yet to be established. Prosurvival signaling, such as through the MAPK cascade, is one way in which cancer cells can evade chemotherapy. We have determined that CCOC exhibits baseline elevated levels of MAPK activity, which increase further upon cisplatin exposure. We have developed a novel MEK inhibitor, URML-3881, to test the effect of MAPK inhibition in CCOC. URML-3881 was found to reduce in vitro CCOC viability through apoptosis and proliferation inhibition, yet it failed to induce in vivo tumor regression. Similarly, cisplatin alone had minimal impact on tumor growth, but remark

SUBMITTER: Rowswell-Turner RB 

PROVIDER: S-EPMC6517847 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature