Targeting SHP1 and SHP2 to suppress tumors and enhance immunosurveillance

Trends Cell Biol. 2025 Aug;35(8):667-677. doi: 10.1016/j.tcb.2024.10.008. Epub 2024 Nov 21.

Abstract

The nonreceptor tyrosine phosphatases (PTPS) SHP1 and SHP2 have crucial roles in dephosphorylating an array of substrates involved in pathways comprising receptor tyrosine kinases (RTKs) and immune receptors. This regulation maintains a delicate balance between the activation and inhibition of signal transduction, ensuring appropriate biological outcomes. In this review, we summarize research focused on elucidating the functions of SHP1 and SHP2 in hematopoiesis, immune regulation, and tumor biology, emphasizing recent findings related to cancer-driven immune evasion. Furthermore, we highlight the significant effects of SHP1 and SHP2 inhibitors in enhancing cancer treatment, specifically through the facilitation of chemotherapy and augmentation of immune activation.

Keywords: SHP1; SHP2; chemoresistance; immune checkpoint; immunosurveillance; receptor tyrosine kinase; signal transduction; tumorigenesis.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Immunologic Surveillance* / drug effects
  • Molecular Targeted Therapy
  • Neoplasms* / drug therapy
  • Neoplasms* / enzymology
  • Neoplasms* / immunology
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11* / antagonists & inhibitors
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11* / metabolism
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6* / antagonists & inhibitors
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6* / metabolism
  • Signal Transduction

Substances

  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6