Inhibitors of the mammalian target of rapamycin

Expert Opin Investig Drugs. 2005 Mar;14(3):313-28. doi: 10.1517/13543784.14.3.313.


The mammalian target of rapamycin (mTOR) is a downstream protein kinase of the phosphatidylinositol 3'-kinase-Akt signalling pathway. As a result of its position within this pathway and its central role in controlling cellular growth, mTOR is viewed as an important target for anticancer therapeutics development. Currently, the mTOR inhibitor rapamycin (sirolimus, Wyeth) and its derivatives temsirolimus (CCI-779, Wyeth), everolimus (RAD-001, Novartis Pharma AG) and AP-23573 (Ariad Pharmaceuticals) are being evaluated in cancer clinical trials. Preclinical studies suggest that sensitivity to mTOR inhibition may correlate with aberrant activation of the phosphatidylinositol 3'-kinase pathway and/or with aberrant expression of cell-cycle regulatory or antiapoptotic proteins. Clinical trial results show that mTOR inhibitors are generally well tolerated and may induce prolonged stable disease and even tumour regressions in a subset of patients. Questions remain regarding optimal dose, schedule, patient selection and combination strategies for this novel class of agents.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Clinical Trials as Topic / statistics & numerical data
  • Drugs, Investigational / therapeutic use*
  • Humans
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein Kinases / metabolism*
  • TOR Serine-Threonine Kinases


  • Antineoplastic Agents
  • Drugs, Investigational
  • Protein Kinase Inhibitors
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases