Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer

@article{Thomas2006HypoxiainducibleFD,
  title={Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer},
  author={George V Thomas and Chris Tran and Ingo K. Mellinghoff and Derek S. Welsbie and E. B. Chan and Barbara J. Fueger and Johannes G Czernin and Charles L Sawyers},
  journal={Nature Medicine},
  year={2006},
  volume={12},
  pages={122-127}
}
Inhibitors of the kinase mammalian target of rapamycin (mTOR) have shown sporadic activity in cancer trials, leading to confusion about the appropriate clinical setting for their use. Here we show that loss of the Von Hippel-Lindau tumor suppressor gene (VHL) sensitizes kidney cancer cells to the mTOR inhibitor CCI-779 in vitro and in mouse models. Growth arrest caused by CCI-779 correlates with a block in translation of mRNA encoding hypoxia-inducible factor (HIF1A), and is rescued by… CONTINUE READING
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