New Targets for Therapy in Breast Cancer: Mammalian Target of Rapamycin (mTOR) Antagonists

Breast Cancer Res. 2004;6(5):219-24. doi: 10.1186/bcr927. Epub 2004 Aug 12.

Abstract

Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (PI3K) pathway, which is involved in multiple biologic functions such as transcriptional and translational control. mTOR is a downstream mediator in the PI3K/Akt signaling pathway and plays a critical role in cell survival. In breast cancer this pathway can be activated by membrane receptors, including the HER (or ErbB) family of growth factor receptors, the insulin-like growth factor receptor, and the estrogen receptor. There is evidence suggesting that Akt promotes breast cancer cell survival and resistance to chemotherapy, trastuzumab, and tamoxifen. Rapamycin is a specific mTOR antagonist that targets this pathway and blocks the downstream signaling elements, resulting in cell cycle arrest in the G1 phase. Targeting the Akt/PI3K pathway with mTOR antagonists may increase the therapeutic efficacy of breast cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacology*
  • Antibiotics, Antineoplastic / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Cell Cycle
  • Humans
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Kinase Inhibitors*
  • Protein Kinases*
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Signal Transduction
  • Sirolimus / analogs & derivatives*
  • Sirolimus / pharmacology*
  • Sirolimus / therapeutic use
  • TOR Serine-Threonine Kinases

Substances

  • Antibiotics, Antineoplastic
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • temsirolimus
  • Protein Kinases
  • Phosphatidylinositol 3-Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Sirolimus