Predicted Mechanisms of Resistance to mTOR Inhibitors

Br J Cancer. 2006 Oct 23;95(8):955-60. doi: 10.1038/sj.bjc.6603353. Epub 2006 Sep 5.

Abstract

The serine/threonine kinase, mTOR (mammalian Target of Rapamycin) has become a focus for cancer drug development. Rapamycins are highly specific inhibitors of mTOR and potently suppress tumour cell growth by retarding cells in G1 phase or potentially inducing apoptosis. Currently, both rapamycin and several analogues are being evaluated as anticancer agents in clinical trials. Results indicate that many human cancers have intrinsic resistance and tumours initially sensitive to rapamycins become refractory, demonstrating acquired resistance. Here, we consider mechanisms of resistance to inhibitors of mTOR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Cycle / drug effects
  • Drug Resistance, Neoplasm*
  • Humans
  • Models, Biological
  • Molecular Structure
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Neoplasms / pathology
  • Protein Kinase Inhibitors / analogs & derivatives
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein Kinases / metabolism*
  • Sirolimus / analogs & derivatives
  • Sirolimus / chemistry
  • Sirolimus / therapeutic use*
  • TOR Serine-Threonine Kinases

Substances

  • Protein Kinase Inhibitors
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus