Lysophosphatidic acid (LPA) as a pro-fibrotic and pro-oncogenic factor: a pivotal target to improve the radiotherapy therapeutic index

Oncotarget. 2017 Jun 27;8(26):43543-43554. doi: 10.18632/oncotarget.16672.

Abstract

Radiation-induced fibrosis is widely considered as a common but forsaken phenomenon that can lead to clinical sequela and possibly vital impairments. Lysophosphatidic acid is a bioactive lipid involved in fibrosis and probably in radiation-induced fibrosis as suggested in recent studies. Lysophosphatidic acid is also a well-described pro-oncogenic factor, involved in carcinogenesis processes (proliferation, survival, angiogenesis, invasion, migration). The present review highlights and summarizes the links between lysophosphatidic acid and radiation-induced fibrosis, lysophosphatidic acid and radioresistance, and proposes lysophosphatidic acid as a potential central actor of the radiotherapy therapeutic index. Besides, we hypothesize that following radiotherapy, the newly formed tumour micro-environment, with increased extracellular matrix and increased lysophosphatidic acid levels, is a favourable ground to metastasis development. Lysophosphatidic acid could therefore be an exciting therapeutic target, minimizing radio-toxicities and radio-resistance effects.

Keywords: cancer; fibrosis; lysophosphatidic acid; proliferation; radiation therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers
  • Cell Transformation, Neoplastic / chemically induced*
  • Fibrosis / etiology*
  • Fibrosis / metabolism
  • Fibrosis / pathology
  • Humans
  • Lysophospholipids / adverse effects*
  • Neoplasms / complications
  • Neoplasms / etiology
  • Neoplasms / pathology
  • Neoplasms / radiotherapy
  • Radiation Tolerance / drug effects
  • Radiation, Ionizing
  • Radiotherapy / adverse effects
  • Radiotherapy / methods
  • Signal Transduction
  • Therapeutic Index

Substances

  • Biomarkers
  • Lysophospholipids
  • lysophosphatidic acid