Phosphatidylserine receptor-targeting therapies for the treatment of cancer

Arch Pharm Res. 2019 Jul;42(7):617-628. doi: 10.1007/s12272-019-01167-4. Epub 2019 Jun 6.

Abstract

Asymmetric distribution of phospholipids across the plasma membrane is a unique characteristic of eukaryotic cells. Phosphatidylcholine and sphingomyelin are exposed in the outer leaflet, and phosphatidylserine (PS) is predominantly located in the inner leaflet. Redistribution of PS to the cell surface can be observed in several physiological conditions, such as apoptosis and platelet activation, or in pathological conditions, such as the release of microvesicles/exosomes from tumor tissues. PS binding to the phosphatidylserine receptor (PSR) on immune cells initiates immunosuppressive pathways that can lead to immune evasion by cancer cells. Conversely, PSR activation of cancer cells plays an important role in their survival, proliferation and metastasis. Herein, we briefly summarize both recent advances in our understanding of the pathological roles of PS and its receptor in cancer biology, as well as relevant pharmacological approaches.

Keywords: Cancer; Phosphatidylserine; Phosphatidylserine receptor; TAM receptor.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinases / metabolism
  • Receptors, Cell Surface / antagonists & inhibitors*
  • Receptors, Cell Surface / metabolism
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Receptors, Cell Surface
  • Small Molecule Libraries
  • phosphatidylserine receptor
  • Protein Kinases