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Updated: Oct 5, 2025

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

6.3K

Inhibition of SHP2 as an approach to block RAS-driven cancers

Yu-Ting Chou1, Trever G Bivona1

  • 1Department of Medicine, Division of Hematology and Oncology, and The Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA, United States.

Advances in Cancer Research
|February 1, 2022
PubMed

Insights

SHP2 (PTPN11) is crucial in RAS/MAPK signaling for cancer growth. Allosteric SHP2 inhibitors offer new therapeutic potential for RAS-driven cancers, overcoming previous challenges with SHP2-targeted drugs.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • SHP2 (PTPN11) is a non-receptor protein tyrosine phosphatase vital for RAS/MAPK signaling.
  • SHP2 acts upstream of RAS, promoting oncogenic signaling and tumor growth.
  • Historically, SHP2 was considered undruggable due to issues with active-site inhibitors.

Purpose of the Study:

  • To review the role of SHP2 in RAS-driven cancers.
  • To discuss the therapeutic potential of novel allosteric SHP2 inhibitors.
  • To highlight SHP2 as a target for blocking RAS-driven oncogenic signaling.

Main Methods:

  • Literature review of SHP2 function in cancer.
  • Analysis of recent developments in allosteric SHP2 inhibitor research.
  • Summary of preclinical and clinical data for SHP2 inhibitors.

Main Results:

  • Allosteric SHP2 inhibitors demonstrate high potency and efficacy in preclinical cancer models.
  • These inhibitors effectively block signal transduction from receptor tyrosine kinases (RTKs) to RAS/MAPK.
  • Clinical trials are underway to evaluate the safety and efficacy of these allosteric inhibitors.

Conclusions:

  • Allosteric SHP2 inhibitors represent a promising therapeutic strategy for RAS-driven cancers.
  • They overcome limitations of previous SHP2-targeting approaches.
  • Targeting SHP2 offers a potential avenue to address resistance seen with other RAS inhibitors.
Keywords:
Allosteric SHP2 inhibitorCombination therapyPTPPTPN11RASSHP2

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