title: Lysophosphatidic acid (LPA) as a pro-fibrotic and pro-oncogenic factor: a pivotal target to improve the radiotherapy therapeutic index.
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.
authors.affiliation: Radiotherapy Department, Lucien Neuwirth Cancer Institute, Saint-Priest-en-Jarez, France.|Cellular and Molecular Radiobiology Laboratory, CNRS UMR 5822, IPNL, Villeurbanne, France.
authors.forename: Chloé
authors.initials: C
authors.lastname: Rancoule
authors.affiliation: Radiotherapy Department, Lucien Neuwirth Cancer Institute, Saint-Priest-en-Jarez, France.|Cellular and Molecular Radiobiology Laboratory, CNRS UMR 5822, IPNL, Villeurbanne, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Espenel
authors.affiliation: Radiotherapy Department, Lucien Neuwirth Cancer Institute, Saint-Priest-en-Jarez, France.
authors.forename: Jane-Chloé
authors.initials: JC
authors.lastname: Trone
authors.affiliation: Radiotherapy Department, Lucien Neuwirth Cancer Institute, Saint-Priest-en-Jarez, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Langrand-Escure
authors.affiliation: Radiotherapy Department, Lucien Neuwirth Cancer Institute, Saint-Priest-en-Jarez, France.|Cellular and Molecular Radiobiology Laboratory, CNRS UMR 5822, IPNL, Villeurbanne, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Vallard
authors.affiliation: Radiotherapy Department, Lucien Neuwirth Cancer Institute, Saint-Priest-en-Jarez, France.
authors.forename: Amel
authors.initials: A
authors.lastname: Rehailia-Blanchard
authors.affiliation: Radiotherapy Department, Lucien Neuwirth Cancer Institute, Saint-Priest-en-Jarez, France.
authors.forename: Anis
authors.initials: A
authors.lastname: El Meddeb Hamrouni
authors.affiliation: Radiotherapy Department, Lucien Neuwirth Cancer Institute, Saint-Priest-en-Jarez, France.
authors.forename: Yaxiong
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Radiotherapy Department, Lucien Neuwirth Cancer Institute, Saint-Priest-en-Jarez, France.|Cellular and Molecular Radiobiology Laboratory, CNRS UMR 5822, IPNL, Villeurbanne, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Guy
authors.affiliation: Radiotherapy Department, Lucien Neuwirth Cancer Institute, Saint-Priest-en-Jarez, France.
authors.forename: Majed
authors.initials: M
authors.lastname: Ben-Mrad
authors.affiliation: Radiotherapy Department, Lucien Neuwirth Cancer Institute, Saint-Priest-en-Jarez, France.|Cellular and Molecular Radiobiology Laboratory, CNRS UMR 5822, IPNL, Villeurbanne, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Magné
mesh_terms: D000818:Animals; D015415:Biomarkers; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D005355:Fibrosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008246:Lysophospholipids / Q000009:adverse effects*; D009369:Neoplasms / Q000150:complications / Q000209:etiology / Q000473:pathology / Q000532:radiotherapy; D011836:Radiation Tolerance / Q000187:drug effects; D011839:Radiation, Ionizing; D011878:Radiotherapy / Q000009:adverse effects / Q000379:methods; D015398:Signal Transduction; D000076162:Therapeutic Index
chemical_list: D015415:Biomarkers; D008246:Lysophospholipids; C032881:lysophosphatidic acid
keywords: cancer; fibrosis; lysophosphatidic acid; proliferation; radiation therapy