Targeting PP2A in cancer: Combination therapies

Biochim Biophys Acta Mol Cell Res. 2019 Jan;1866(1):51-63. doi: 10.1016/j.bbamcr.2018.08.020. Epub 2018 Sep 1.

Abstract

The serine/threonine phosphatase PP2A regulates a vast portion of the phosphoproteome including pathways involved in apoptosis, proliferation and DNA damage response and PP2A inactivation is a vital step in malignant transformation. Many groups have explored the therapeutic venue of combining PP2A reactivation with kinase inhibition to counteract the very changes in tumor suppressors and oncogenes that lead to cancer development. Conversely, inhibition of PP2A to complement chemotherapy and radiation-induced cancer cell death is also an area of active investigation. Here we review the studies that utilize PP2A targeted agents as combination therapy in cancer. A potential role for PP2A in tumor immunity is also highlighted.

Keywords: Cell signaling; Protein phosphatases; Targeted therapies.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Apoptosis / physiology
  • Cell Proliferation / physiology
  • DNA Repair / physiology
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Molecular Targeted Therapy / methods
  • Neoplasm Proteins / metabolism
  • Neoplasms / metabolism
  • Neoplasms / physiopathology
  • Neoplasms / therapy
  • Phosphoprotein Phosphatases / metabolism
  • Phosphoprotein Phosphatases / physiology
  • Protein Phosphatase 2 / genetics*
  • Protein Phosphatase 2 / metabolism*
  • Protein Phosphatase 2 / physiology*
  • Protein Subunits / physiology
  • Signal Transduction / physiology

Substances

  • Antineoplastic Agents
  • Neoplasm Proteins
  • Protein Subunits
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2