Therapeutic potential of mTOR inhibitors for targeting cancer stem cells

Br J Clin Pharmacol. 2016 Nov;82(5):1180-1188. doi: 10.1111/bcp.12844. Epub 2015 Dec 26.

Abstract

The mammalian target of rapamycin (mTOR) pathway is aberrantly activated in many cancer types. As the intricate network of regulatory mechanisms controlling mTOR activity is uncovered, more refined drugs are designed and tested in clinical trials. While first generation mTOR inhibitors have failed to show clinical efficacy due partly to the feedback relief of oncogenetic circuits, newly developed inhibitors show greater promise as anti-cancer agents. An effective drug must defeat the cancer stem cells (CSCs) while sparing the normal stem cells. Due to its opposing role on normal and malignant stem cells, mTOR lends itself very well as a therapeutic target. Indeed, a preferential inhibitory effect on CSCs has already been shown for some mTOR inhibitors. These results provide a compelling rationale for the clinical development of mTOR-targeted therapies.

Keywords: cancer stem cells, drug resistance; mTOR; personalized medicine; tumour heterogeneity.

Publication types

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

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Humans
  • Molecular Targeted Therapy / methods*
  • Neoplastic Stem Cells / drug effects*
  • Protein Kinase Inhibitors / therapeutic use*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*

Substances

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