I initially chose two cell lines that represented 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. The cells were treated with 1,912 oncology-focused drugs using a 48 hr cell proliferation assay with an ATP-based readout (CellTiterGlo), and activity of the compounds in a dose response manner was calculated. Encouraged by the preliminary results showing HSP90 inhibitors, topoisomerase I inhibitors, and HDAC inhibitors all being effective, we extended the screen to 8 bladder cancer cell lines. We found similar results except now combinations were also explored. Some of the combinations that we hope to explore in animal models include a novel SMAC mimetic + gemcitabine or mitomycin C. We also identified 8 novel agents that may function as intravesical agents and are currently evaluating their use as well. Finally, we identified a topotecan derivative (SN-38) from the screen that looks promising. We are asking our collaborators to bind existing Pan-IR700 conjugate to SN-38 to increase the cytotoxicity of this new conjugate.
| 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 |
