mTOR kinase inhibitors as potential cancer therapeutic drugs

Cancer Lett. 2013 Oct 28;340(1):1-8. doi: 10.1016/j.canlet.2013.06.017. Epub 2013 Jun 20.


The mammalian target of rapamycin (mTOR) plays a critical role in the positive regulation of cell growth and survival primarily through direct interaction with raptor (forming mTORC complex 1; mTORC1) or rictor (forming mTOR complex 2; mTORC2). The mTOR axis is often activated in many types of cancer and thus has become an attractive cancer therapeutic target. The modest clinical anticancer activity of conventional mTOR allosteric inhibitors, rapamycin and its analogs (rapalogs), which preferentially inhibit mTORC1, in most types of cancer, has encouraged great efforts to develop mTOR kinase inhibitors (TORKinibs) that inhibit both mTORC1 and mTORC2, in the hope of developing a novel generation of mTOR inhibitors with better therapeutic efficacy than rapalogs. Several TORKinibs have been developed and actively studied pre-clinically and clinically. This review will highlight recent advances in the development and research of TORKinibs and discuss some potential issues or challenges in this area.

Keywords: Cancer; Inhibitors; Kinase; mTOR.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Clinical Trials as Topic
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use
  • Signal Transduction
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*


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