I have chosen two cell lines that represent the spectrum of bladder cancer cell lines: UMUC-3 and RT4. The former is a mesenchymal, high-grade, and a luminal tumor. The latter is an epithelial, low-grade, and a basal tumor. In summary, these cell lines represent some of the most difficult bladder tumors to treat but have unique features along the EMT spectrum and sensitivity to EGFR-based therapy that will help identify subtle differences among therapeutics. However, since they are relatively resistant to cisplatinum-based chemotherapy, they will hopefully identify new targets for bladder tumors refractory to standard of care therapy. Furthermore, these cell lines have been well-characterized in the literature and have sequenced in publically available cancer cell line databases. Using the platform established by Lou Stadt's group, we will screen 2000+ drugs against these cell lines to identify a novel agent. We will then explore in detail therapeutics identified by this strategy.
Ahmed, Kamran; Khan, Shahid A; Hayn, Matthew H et al. (2014) Analysis of intracorporeal compared with extracorporeal urinary diversion after robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium. Eur Urol 65:340-7 |