Turcotte S~Giaccia AJ, 2008

Pubmed ID 18598947
Title A molecule targeting VHL-deficient renal cell carcinoma that induces autophagy.
Authors Sandra Turcotte, Denise A Chan, Patrick D Sutphin, Michael P Hay, William A Denny, Amato J Giaccia
Abstract 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.
Citation Cancer Cell 2008; 14:90-102

Datasets

Download the list of datasets
Paper Phenotype Condition Reference Collection Tested mutants Data Details
Turcotte S~Giaccia AJ, 2008 growth (pooled CFU) STF-62247 [0–100 μM] hom ~4,728 Discrete

Curation history

Tested strains

Oct. 25, 2016 To request.
Oct. 27, 2016 Request sent.
April 25, 2017 Request sent.
April 25, 2017 Not available.

Data

Oct. 25, 2016 To request.
Oct. 27, 2016 Request sent.
April 25, 2017 Request sent.
April 25, 2017 Not available.
April 25, 2017 Ready to load.
April 29, 2017 Loaded.