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Ref Type Journal Article
PMID (18598947)
Authors Turcotte S, Chan DA, Sutphin PD, Hay MP, Denny WA, Giaccia AJ
Title A molecule targeting VHL-deficient renal cell carcinoma that induces autophagy.
Journal Vol Issue Date Pages Journal Short Title
Cancer cell 14 1 2008 Jul 8 90-102 Cancer Cell
URL
Abstract Text 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.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
VHL negative renal cell carcinoma sensitive STF-62247 Preclinical Actionable In a preclinical study, STF-62247 induced selective cytotoxicity and inhibited tumor growth of renal cell carcinoma cells lacking VHL (PMID: 18769110, PMID: 18598947). 18769110 18598947