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 been sequenced in publically available cancer cell line databases. Using the platform established by Lou Stadt's group, we screened epithelial (RT4) and mesenchymal (UMUC-3) bladder cancer cell lines against 1,912 oncology-focused drugs using a 48 hr cell proliferation assay with an ATP-based readout (CellTiterGlo), and determined the activity of the compounds in a dose response manner. We identified three compounds that achieved a full dose response - Bortezomib (Proteasome inhibitor) , Doxorubicin, and Idarubicin Hydrochloride (Topoisomerase inhibitors) and analyzed these 3 drugs in 3 different bladder cancer cell lines (UMUC-5, T24, and 5637) using the MTS assay) to determine the IC50s of these drugs in multiple bladder cancer cell lines. Results are to be reported at an upcoming national meeting.
| 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 |
