An expanding role for mTOR in cancer

Trends Mol Med. 2005 Aug;11(8):353-61. doi: 10.1016/j.molmed.2005.06.007.

Abstract

Rapamycin, a valuable drug with diverse clinical applications, inhibits mTOR (mammalian target of rapamycin), which is a protein kinase that controls cell growth by regulating many cellular processes, including protein synthesis and autophagy. The sensitivity of select tumor cells to rapamycin has ignited considerable excitement over its potential as an anti-cancer therapeutic. Recent findings identified a rapamycin-insensitive function of mTOR in regulating a cell-survival pathway that is hyperactive in many cancers, particularly those with elevated PtdIns3K signaling or harboring mutations in the tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10). These new findings suggest that targeting this function of mTOR might have broader applications in cancer therapy. In this article, we re-evaluate mTOR signaling, suggesting a more central role for mTOR in cancers with defective PtdIns3K-PTEN signaling and conceptually discuss these implications in the context of drug discovery.

Publication types

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

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacology*
  • Antibiotics, Antineoplastic / therapeutic use
  • Drosophila
  • Genes, Tumor Suppressor / drug effects
  • Humans
  • Mutation
  • Neoplasms / drug therapy
  • Neoplasms / physiopathology*
  • Protein Kinases / drug effects
  • Protein Kinases / physiology*
  • Protein-Serine-Threonine Kinases / physiology
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-akt
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Sirolimus / pharmacology*
  • Sirolimus / therapeutic use
  • TOR Serine-Threonine Kinases
  • Up-Regulation

Substances

  • Antibiotics, Antineoplastic
  • Proto-Oncogene Proteins
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Sirolimus