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

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.

Molecular profile of pure squamous cell carcinoma of the bladder identifies major roles for OSMR and YAP signalling.

Pure squamous cell carcinoma (SCC) is the most common pure variant form of bladder cancer, found in 2-5% of cases. It often presents late and is unresponsive to cisplatin-based chemotherapy. The molecular features of these tumours have not been elucidated in detail.