Lysophosphatidic acid (LPA) as a pro-fibrotic and pro-oncogenic factor: a pivotal target to improve the radiotherapy therapeutic index
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Chloé Rancoule1,2, Sophie Espenel1,2, Jane-Chloé Trone1, Julien Langrand-Escure1, Alexis Vallard1,2, Amel Rehailia-Blanchard1, Anis El Meddeb Hamrouni1, Yaxiong Xia1, Jean-Baptiste Guy1,2, Majed Ben-Mrad1 and Nicolas Magné1,2
1 Radiotherapy Department, Lucien Neuwirth Cancer Institute, Saint-Priest-en-Jarez, France
2 Cellular and Molecular Radiobiology Laboratory, CNRS UMR 5822, IPNL, Villeurbanne, France
Nicolas Magné, email:
Keywords: cancer, radiation therapy, fibrosis, lysophosphatidic acid, proliferation
Received: November 08, 2016 Accepted: March 08, 2017 Published: March 29, 2017
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.
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