Current development of mTOR inhibitors as anticancer agents

Nat Rev Drug Discov. 2006 Aug;5(8):671-88. doi: 10.1038/nrd2062.

Abstract

Mammalian target of rapamycin (mTOR) is a kinase that functions as a master switch between catabolic and anabolic metabolism and as such is a target for the design of anticancer agents. The most established mTOR inhibitors--rapamycin and its derivatives--showed long-lasting objective tumour responses in clinical trials, with CCI-779 being a first-in-class mTOR inhibitor that improved the survival of patients with advanced renal cell carcinoma. This heralded the beginning of extensive clinical programmes to further evaluate mTOR inhibitors in several tumour types. Here we review the clinical development of this drug class and look at future prospects for incorporating these agents into multitarget or multimodality strategies against cancer.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / physiology
  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Drug Resistance, Neoplasm
  • Epigenesis, Genetic
  • Humans
  • Neoplasms / drug therapy*
  • Neovascularization, Pathologic / drug therapy
  • PTEN Phosphohydrolase / genetics
  • Phosphatidylinositol 3-Kinases / physiology
  • Phosphoproteins / physiology
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein Kinases* / physiology
  • Proto-Oncogene Proteins c-akt / physiology
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases

Substances

  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents
  • EIF4EBP1 protein, human
  • Phosphoproteins
  • Protein Kinase Inhibitors
  • Protein Kinases
  • Phosphatidylinositol 3-Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase