{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Dasari SK"],"funding":["NIH-NCI","Dunwoody Fund","CPRIT-funded Combinatorial Drug Discovery Program","NCI NIH HHS","Frank McGraw Memorial Chair in Cancer Research","NIH","Gordon Fund","American Cancer Society Research Professor Award"],"pagination":["3915"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9962847"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["24(4)"],"pubmed_abstract":["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 mo"],"journal":["International journal of molecular sciences"],"pubmed_title":["Combination of EphA2- and Wee1-Targeted Therapies in Endometrial Cancer."],"pmcid":["PMC9962847"],"funding_grant_id":["P50 CA098258","R35 CA209904","P30 CA016672","RP200668","U01 CA213759","R35CA209904","RP150578","CA098258"],"pubmed_authors":["Sood AK","Sobieski M","Bayraktar E","Nguyen N","Joseph R","Rodriguez-Aguayo C","Liu Y","Mangala LS","Powell RT","Westin SN","Chowdhury MA","Umamaheswaran S","Lopez-Berestein G","Amero P","Dasari SK","Wu Y","Stephan C"],"additional_accession":[]},"is_claimable":false,"name":"Combination of EphA2- and Wee1-Targeted Therapies in Endometrial Cancer.","description":"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 mo","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Feb","modification":"2026-04-08T13:29:35.523Z","creation":"2024-12-04T13:09:48.844Z"},"accession":"S-EPMC9962847","cross_references":{"pubmed":["36835335"],"doi":["10.3390/ijms24043915"]}}