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Targeting Lysophosphatidic Acid in Cancer: The Issues in Moving from Bench to Bedside

Department of Obstetrics and Gynecology, Indiana University School of Medicine, 950 W. Walnut Street R2-E380, Indianapolis, IN 46202, USA
Cancers 2019, 11(10), 1523; https://doi.org/10.3390/cancers11101523
Received: 28 August 2019 / Revised: 2 October 2019 / Accepted: 8 October 2019 / Published: 10 October 2019
(This article belongs to the Special Issue Lysophosphatidic Acid Signalling in Cancer)
Since the clear demonstration of lysophosphatidic acid (LPA)’s pathological roles in cancer in the mid-1990s, more than 1000 papers relating LPA to various types of cancer were published. Through these studies, LPA was established as a target for cancer. Although LPA-related inhibitors entered clinical trials for fibrosis, the concept of targeting LPA is yet to be moved to clinical cancer treatment. The major challenges that we are facing in moving LPA application from bench to bedside include the intrinsic and complicated metabolic, functional, and signaling properties of LPA, as well as technical issues, which are discussed in this review. Potential strategies and perspectives to improve the translational progress are suggested. Despite these challenges, we are optimistic that LPA blockage, particularly in combination with other agents, is on the horizon to be incorporated into clinical applications. View Full-Text
Keywords: Autotaxin (ATX); ovarian cancer (OC); cancer stem cell (CSC); electrospray ionization tandem mass spectrometry (ESI-MS/MS); G-protein coupled receptor (GPCR); lipid phosphate phosphatase enzymes (LPPs); lysophosphatidic acid (LPA); phospholipase A2 enzymes (PLA2s); nuclear receptor peroxisome proliferator-activated receptor (PPAR); sphingosine-1 phosphate (S1P) Autotaxin (ATX); ovarian cancer (OC); cancer stem cell (CSC); electrospray ionization tandem mass spectrometry (ESI-MS/MS); G-protein coupled receptor (GPCR); lipid phosphate phosphatase enzymes (LPPs); lysophosphatidic acid (LPA); phospholipase A2 enzymes (PLA2s); nuclear receptor peroxisome proliferator-activated receptor (PPAR); sphingosine-1 phosphate (S1P)
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Xu, Y. Targeting Lysophosphatidic Acid in Cancer: The Issues in Moving from Bench to Bedside. Cancers 2019, 11, 1523.

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