Opop schreef op 18 maart 2018 14:31:
Coming of Age for Autotaxin and Lysophosphatidate Signaling: Clinical Applications for Preventing,Detecting and Targeting Tumor-Promoting Inflammation. Published: 15 March 2018
In this review, we will summarize recent advances made in understanding LPA signaling with respect to chronic inflammation and cancer.
Overall, LPA, a simplemolecule thatmediates 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.Pharmacological Targeting of LPA-Mediated Inflammation and Cancer Progression:
Blz 13, 7.4. Inhibitors of LPA Signaling Entering into Clinical Trials:
The number of inhibitors against LPA signaling has now reached a critical mass, such that the first ATX and LPA receptor inhibitors have entered clinical trials  (Table 1). Galapagos NV have tested the first ATX inhibitor, GLPG1690, currently in Phase II trials for idiopathic pulmonary
fibrosis (IPF)  (Table 1). In a blelomycin-induced pulmonary fibrosis murine model, an analog of GLPG1690 reduced extracellular matrix deposition in the lung by nearly 50% and reduced the concentrations 18:2-LPA in bronchoalveolar lavage fluid by nearly 70%
Conclusions: In summary, we are at an exciting time where several therapeutics are in advanced clinical trials for blocking LPA signaling and inflammation. These agents are generally well tolerated and they could be tested as novel strategies for improving the effectiveness of existing cancer therapies. These approaches should be applicable to a wide variety of cancers since they target the tumor environment, which should be relatively independent of the specific mutation in the cancer cells. Overall, as mitigators of chronic
inflammation, inhibitors of LPA signaling could become viable therapeutic modalities for preventing cancer initiation, maintaining the efficacy of chemotherapy and radiotherapy and prolonging remission.www.google.nl/url?sa=t&rct=j&...
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