Elucidating mechanisms of resistance to FGFR inhibitors in endometrial cancer

Abstract

Abstract Preclinical studies by our lab and others have demonstrated Fibroblast Growth Factor Receptor (FGFR) inhibition is a viable therapeutic strategy in FGFR2-mutant endometrial cancer (EC). A significant clinical issue that we aim to address is that of intrinsic and acquired resistance to anti-FGFR therapeutics in the context of EC. Using mutagenesis screens, we have identified mutations in the FGFR2 kinase domain that cause resistance to the FGFR inhibitors dovitinib and NVP-BGJ398 and explore the mechanism of action of the drug-resistant mutations. We previously reported the N550K and V565I mutations caused resistance to dovitinib. The sensitivity/resista..