کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2108410 | 1083778 | 2008 | 13 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: A Molecule Targeting VHL-Deficient Renal Cell Carcinoma that Induces Autophagy A Molecule Targeting VHL-Deficient Renal Cell Carcinoma that Induces Autophagy](/preview/png/2108410.png)
SummaryRenal 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.
Journal: - Volume 14, Issue 1, 8 July 2008, Pages 90–102