Druggable cancer phosphatases

Sci Transl Med. 2021 Apr 7;13(588):eabe2967. doi: 10.1126/scitranslmed.abe2967.


The phosphorylation status of oncoproteins is regulated by both kinases and phosphatases. Kinase inhibitors are rarely sufficient for successful cancer treatment, and phosphatases have been considered undruggable targets for cancer drug development. However, innovative pharmacological approaches for targeting phosphatases have recently emerged. Here, we review progress in the therapeutic targeting of oncogenic Src homology region 2 domain-containing phosphatase-2 (SHP2) and tumor suppressor protein phosphatase 2A (PP2A) and select other druggable oncogenic and tumor suppressor phosphatases. We describe the modes of action for currently available small molecules that target phosphatases, their use in drug combinations, and advances in clinical development toward future cancer therapies.

Publication types

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

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Genes, Tumor Suppressor
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Phosphorylation
  • Protein Phosphatase 2* / metabolism
  • SH2 Domain-Containing Protein Tyrosine Phosphatases* / metabolism


  • Antineoplastic Agents
  • Protein Phosphatase 2
  • SH2 Domain-Containing Protein Tyrosine Phosphatases