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2018 ; 10
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English Wikipedia
Coming of Age for Autotaxin and Lysophosphatidate Signaling: Clinical
Applications for Preventing, Detecting and Targeting Tumor-Promoting
Inflammation
#MMPMID29543710
Cancers (Basel)
2018[Mar]; 10
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show ga
A quarter-century after the discovery of autotaxin in cell culture, the
autotaxin-lysophosphatidate (LPA)-lipid phosphate phosphatase axis is now a
promising clinical target for treating chronic inflammatory conditions,
mitigating fibrosis progression, and improving the efficacy of existing cancer
chemotherapies and radiotherapy. Nearly half of the literature on this axis has
been published during the last five years. In cancer biology, LPA signaling is
increasingly being recognized as a central mediator of the progression of chronic
inflammation in the establishment of a tumor microenvironment which promotes
cancer growth, immune evasion, metastasis, and treatment resistance. In this
review, we will summarize recent advances made in understanding LPA signaling
with respect to chronic inflammation and cancer. We will also provide
perspectives on the applications of inhibitors of LPA signaling in preventing
cancer initiation, as adjuncts extending the efficacy of current cancer
treatments by blocking inflammation caused by either the cancer or the cancer
therapy itself, and by disruption of the tumor microenvironment. Overall, LPA, a
simple molecule that mediates a plethora of biological effects, can be targeted
at its levels of production by autotaxin, LPA receptors or through LPA
degradation by lipid phosphate phosphatases. Drugs for these applications will
soon be entering clinical practice.