The role of RICTOR amplification in targeted therapy and drug resistance

Mol Med. 2020 Feb 10;26(1):20. doi: 10.1186/s10020-020-0146-6.


The emergence of tyrosine kinase inhibitors (TKIs) has changed the current treatment paradigm and achieved good results in recent decades. However, an increasing number of studies have indicated that the complex network of receptor tyrosine kinase (RTK) co-activation could influence the characteristic phenotypes of cancer and the tumor response to targeted treatments. One of strategies to blocking RTK co-activation is targeting the downstream factors of RTK, such as PI3K-AKT-mTOR pathway. RICTOR, a core component of mTORC2, acts as a key effector molecule of the PI3K-AKT pathway; its amplification is often associated with poor clinical outcomes and resistance to TKIs. Here, we discuss the biology of RICTOR in tumor and the prospects of targeting RICTOR as a complementary therapy to inhibit RTK co-activation.

Keywords: Drug resistance; RICTOR; TKIs; mTORC2.

Publication types

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

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Clinical Trials as Topic
  • Drug Resistance, Neoplasm* / drug effects
  • Gene Amplification*
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Rapamycin-Insensitive Companion of mTOR Protein / antagonists & inhibitors
  • Rapamycin-Insensitive Companion of mTOR Protein / genetics*


  • Protein Kinase Inhibitors
  • RICTOR protein, human
  • Rapamycin-Insensitive Companion of mTOR Protein