biostudies-literatureDasari SKNIH-NCIDunwoody FundCPRIT-funded Combinatorial Drug Discovery ProgramNCI NIH HHSFrank McGraw Memorial Chair in Cancer ResearchNIHGordon FundAmerican Cancer Society Research Professor Award3915https://www.ebi.ac.uk/biostudies/studies/S-EPMC9962847biostudies-literatureUnknown24(4)EphA2 tyrosine kinase is upregulated in many cancers and correlated with poor survival of patients, including those with endometrial cancer. EphA2-targeted drugs have shown modest clinical benefit. To improve the therapeutic response to such drugs, we performed a high-throughput chemical screen to discover novel synergistic partners for EphA2-targeted therapeutics. Our screen identified the Wee1 kinase inhibitor, MK1775, as a synergistic partner to EphA2, and this finding was confirmed using both in vitro and in vivo experiments. We hypothesized that Wee1 inhibition would sensitize cells to EphA2-targeted therapy. Combination treatment decreased cell viability, induced apoptosis, and reduced clonogenic potential in endometrial cancer cell lines. In vivo Hec1A and Ishikawa-Luc orthotopic moInternational journal of molecular sciencesCombination of EphA2- and Wee1-Targeted Therapies in Endometrial Cancer.PMC9962847P50 CA098258R35 CA209904P30 CA016672RP200668U01 CA213759R35CA209904RP150578CA098258Sood AKSobieski MBayraktar ENguyen NJoseph RRodriguez-Aguayo CLiu YMangala LSPowell RTWestin SNChowdhury MAUmamaheswaran SLopez-Berestein GAmero PDasari SKWu YStephan CfalseCombination of EphA2- and Wee1-Targeted Therapies in Endometrial Cancer.EphA2 tyrosine kinase is upregulated in many cancers and correlated with poor survival of patients, including those with endometrial cancer. EphA2-targeted drugs have shown modest clinical benefit. To improve the therapeutic response to such drugs, we performed a high-throughput chemical screen to discover novel synergistic partners for EphA2-targeted therapeutics. Our screen identified the Wee1 kinase inhibitor, MK1775, as a synergistic partner to EphA2, and this finding was confirmed using both in vitro and in vivo experiments. We hypothesized that Wee1 inhibition would sensitize cells to EphA2-targeted therapy. Combination treatment decreased cell viability, induced apoptosis, and reduced clonogenic potential in endometrial cancer cell lines. In vivo Hec1A and Ishikawa-Luc orthotopic mo2023-01-01T00:00:00Z2023 Feb2026-04-08T13:29:35.523Z2024-12-04T13:09:48.844ZS-EPMC99628473683533510.3390/ijms24043915