Targeting lysophosphatidic acid-mediated autocrine/paracrine growth as a novel therapeutic approa...
Background: Recent evidence suggests that the lysophosphatidic acid (LPA) axis plays a pivotal role in pathobiology of HCC. In particular, we have demonstrated that the LPA axis acts prevalently in a directional way by supporting both a paracrine and an autocrine loop to sustain tumor growth and progression (Mazzocca et al., Hepatol 2011; Cancer Res 2015).
Hypothesis: The overall hypothesis guiding this application is that the interruption of the LPA axis by novel therapeutical approaches leads to decreased cancer growth. We hypothesize that pharmacological or biological inhibition of LPA will result in an interruption of LPA-mediated autocrine and paracrine mechanisms and the consequent arrest of HCC growth and progression.
We will pursue the following aims:
1.Inhibit the LPA-mediated tumor/CAFs interactions promoting HCC growth progression using pharmacological and biological agents.
2. Target the mechanism by which the LPA/LPAR6 autocrine loop sustains
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