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

  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},
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
Highly Influential
This paper has highly influenced 16 other papers. REVIEW HIGHLY INFLUENTIAL CITATIONS


Publications citing this paper.
Showing 1-10 of 225 extracted citations

Nephrotoxicity of recent anti-cancer agents

Clinical kidney journal • 2014
View 9 Excerpts
Highly Influenced

Temsirolimus: a safety and efficacy review.

Expert opinion on drug safety • 2012
View 6 Excerpts
Highly Influenced

Therapeutic challenges in renal cell carcinoma.

American journal of clinical and experimental urology • 2015
View 3 Excerpts
Highly Influenced

Molecular diagnosis and therapy of kidney cancer.

Annual review of medicine • 2010
View 6 Excerpts
Highly Influenced


Publications referenced by this paper.
Showing 1-10 of 25 references

Molecular determinants of resistance to antiandrogen therapy

Chen, C.D
Nat. Med • 2004

Role of VHL gene mutation in human cancer.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology • 2004

The role of 18F-FDG PET in staging and early prediction of response to therapy of recurrent gastrointestinal stromal tumors

I Gayed
J. Nucl. Med • 2004

Similar Papers

Loading similar papers…