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【Cancer cell】一种靶向VHL缺陷的肾细胞癌的分子可
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.
http://www.cancercell.org/content/article/abstract?uid=PIIS1535610808001943
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WWK-4SXRJ04-D&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=783a63d04bd45af357fd107a8e184bd7 [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-06-17 18:08
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