Disease models

A panel of patient-derived organoid models of bladder cancer could be used to screen therapies for the indication. The panel consists of 22 bladder cancer organoids generated from 16 patient-derived transurethral tumor samples. Sequencing of 468 cancer-associated genes in the organoids showed each had a mutational profile that was representative of a mutational subtype of bladder cancer. In 9 and 11 of the organoids, response to 40 and 10 drug compounds, respectively, correlated with the stage of the parental tumor sample and varied with organoid’s subtype. In an organoid harboring an activating mutation in fibroblast growth factor receptor 3 (FGFR3; CD333) and a nonsense mutation in tuberous sclerosis complex tumor suppressor 1 (TSC1), the FGFR inhibitor erdafitinib plus a mammalian target of rapamycin (mTOR; FRAP; RAFT1) inhibitor tool compound decreased viability compared with either agent alone. Next steps could include determining whether drug responses in the organoids recapitulate the response in bladder cancer patients whose tumors have the corresponding mutational profiles...