Development of resistance to FGFR inhibition in urothelial carcinoma via multiple pathways in vitro.

ABSTRACT: Alterations of fibroblast growth factor receptors (FGFRs) are common in bladder and other cancers and result in disrupted signalling via several pathways. Therapeutics that target FGFRs have now entered the clinic, but, in common with many cancer therapies, resistance develops in most cases. To model this, we derived resistant sublines of two FGFR-driven bladder cancer cell lines by long-term culture with the FGFR inhibitor PD173074 and explored mechanisms using expression profiling and whole-exome sequencing. We identified several resistance-associated molecular profiles. These included HRAS mutation in one case and reversible mechanisms resembling a drug-tolerant persister phenotype in others. Upregulated IGF1R expression in one resistant derivative was associated with sensitivity to lin

SUBMITTER: Pettitt GA 

PROVIDER: S-EPMC10107504 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature