Benefits of mTOR kinase targeting in oncology: pre-clinical evidence with AZD8055

Biochem Soc Trans. 2011 Apr;39(2):456-9. doi: 10.1042/BST0390456.

Abstract

AZD8055 is a small-molecule inhibitor of mTOR (mammalian target of rapamycin) kinase activity. The present review highlights molecular and phenotypic differences between AZD8055 and allosteric inhibitors of mTOR such as rapamycin. Biomarkers, some of which are applicable to clinical studies, as well as biological effects such as autophagy, growth inhibition and cell death are compared between AZD8055 and rapamycin. Potential ways to develop rational combinations with mTOR kinase inhibitors are also discussed. Overall, AZD8055 may provide a better therapeutic strategy than rapamycin and analogues.

Publication types

  • Evaluation Study
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Drug Evaluation, Preclinical
  • Humans
  • Medical Oncology / methods*
  • Molecular Targeted Therapy / methods
  • Morpholines / therapeutic use*
  • Neoplasms / drug therapy*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Sirolimus / analogs & derivatives
  • Sirolimus / pharmacology
  • Sirolimus / therapeutic use
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*

Substances

  • Antineoplastic Agents
  • Morpholines
  • Protein Kinase Inhibitors
  • (5-(2,4-bis((3S)-3-methylmorpholin-4-yl)pyrido(2,3-d)pyrimidin-7-yl)-2-methoxyphenyl)methanol
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus