||A molecule targeting VHL-deficient renal cell carcinoma that induces autophagy.
||Sandra Turcotte, Denise A Chan, Patrick D Sutphin, Michael P Hay, William A Denny, Amato J Giaccia
||Renal cell carcinomas (RCCs) are refractory to standard therapies. The von Hippel-Lindau (VHL) tumor suppressor gene is inactivated in 75% of RCCs. By screening for small molecules selectively targeting VHL-deficient RCC cells, we identified STF-62247. STF-62247 induces cytotoxicity and reduces tumor growth of VHL-deficient RCC cells compared to genetically matched cells with wild-type VHL. STF-62247-stimulated toxicity occurs in a HIF-independent manner through autophagy. Reduction of protein levels of essential autophagy pathway components reduces sensitivity of VHL-deficient cells to STF-62247. Using a yeast deletion pool, we show that loss of proteins involved in Golgi trafficking increases killing by STF-62247. Thus, we have found a small molecule that selectively induces cell death in VHL-deficient cells, representing a paradigm shift for targeted therapy.
||Cancer Cell 2008; 14:90-102
These data may contain errors.
YeastPhenome.org is running in beta version.
The data are available for download, but, as of today, we cannot guarantee lack of errors or code bugs introduced during processing.
This warning will be removed after all cross-checks and validations have been completed.
In the meantime, please, be careful when using the data.