IRS-1: auditing the effectiveness of mTOR inhibitors

Cancer Cell. 2006 Mar;9(3):153-5. doi: 10.1016/j.ccr.2006.02.027.


Rapamycin analogs that inhibit mTOR signaling have antitumor activity against certain lymphomas, but treatment of solid tumors has been less encouraging despite inhibition of mTOR function. Two recent papers give insight into the potential use of mTOR inhibitors. O'Reilly et al. provide evidence that poor tumor response to rapamycins is the result of relieving mTOR-mediated feedback inhibition of insulin receptor substrate 1, and activation of Akt-mediated survival. In the second paper, Kaper et al. address the impact of pathway activation on hypoxia-mediated downregulation of mTOR signaling, raising the possibility that rapalogs could selectively inhibit hypoxic cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Humans
  • Phosphatidylinositol 3-Kinases / drug effects
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Kinases / drug effects*
  • Protein Kinases / metabolism
  • Signal Transduction / physiology*
  • Sirolimus / analogs & derivatives
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases


  • Antineoplastic Agents
  • Protein Kinases
  • Phosphatidylinositol 3-Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus