mTOR Signaling in Cancer and mTOR Inhibitors in Solid Tumor Targeting Therapy

Int J Mol Sci. 2019 Feb 11;20(3):755. doi: 10.3390/ijms20030755.

Abstract

The mammalian or mechanistic target of rapamycin (mTOR) pathway plays a crucial role in regulation of cell survival, metabolism, growth and protein synthesis in response to upstream signals in both normal physiological and pathological conditions, especially in cancer. Aberrant mTOR signaling resulting from genetic alterations from different levels of the signal cascade is commonly observed in various types of cancers. Upon hyperactivation, mTOR signaling promotes cell proliferation and metabolism that contribute to tumor initiation and progression. In addition, mTOR also negatively regulates autophagy via different ways. We discuss mTOR signaling and its key upstream and downstream factors, the specific genetic changes in the mTOR pathway and the inhibitors of mTOR applied as therapeutic strategies in eight solid tumors. Although monotherapy and combination therapy with mTOR inhibitors have been extensively applied in preclinical and clinical trials in various cancer types, innovative therapies with better efficacy and less drug resistance are still in great need, and new biomarkers and deep sequencing technologies will facilitate these mTOR targeting drugs benefit the cancer patients in personalized therapy.

Keywords: PI3K; cancer; inhibitor; mTOR; therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers
  • Clinical Trials as Topic
  • Humans
  • Molecular Targeted Therapy*
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism*
  • Treatment Outcome

Substances

  • Biomarkers
  • Protein Kinase Inhibitors
  • TOR Serine-Threonine Kinases