The role of RICTOR downstream of receptor tyrosine kinase in cancers

Mol Cancer. 2018 Feb 19;17(1):39. doi: 10.1186/s12943-018-0794-0.

Abstract

The importance of the network defined by phosphatidylinositol-3-kinase (PI3K), AKT and mammalian target of rapamycin (mTOR) downstream of Receptor Tyrosine Kinase (RTK) has been known for many years but the central role of RICTOR (rapamycin-insensitive companion of mTOR) in this pathway is only starting to emerge. RICTOR is critical for mTORC2 (the mammalian target of rapamycin complex 2) kinase activity and as such plays a key role downstream of RTK. Alterations of RICTOR have been identified in a number of cancer cell types and its involvement in tumorigenesis has begun to be unraveled recently. Here, we summarize new research into the biology of RICTOR signaling in cancers focusing on tumors with altered RTK. We show that, as a key signaling node and critical effector of RTKs, RICTOR is becoming a valuable therapeutic target in cancer with altered RTK.

Keywords: EGFR; HER2; PDGFR; PI3K; RICTOR; RTK; VEGFR; mTOR; mTOR inhibitors; mTORC2.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Rapamycin-Insensitive Companion of mTOR Protein / genetics
  • Rapamycin-Insensitive Companion of mTOR Protein / metabolism*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Antineoplastic Agents
  • Rapamycin-Insensitive Companion of mTOR Protein
  • Receptor Protein-Tyrosine Kinases
  • TOR Serine-Threonine Kinases