The PDGFRβ-dependent feedback loop compromises the anti-tumor activity of rapamycin in HCC.

<p>In HCC, PDGFRβ is the major negative-regulation target of mTOR. Rapamycin paradoxically up-regulates the expression and phosphorylation of PDGFRβ, then subsequently induces activation of PI3K/AKT and MAPK pathway. This PDGFRβ-dependent feedback loop compromises the anti-tumor activity of rapamycin, and blockade of this feedback loop by sorafenib enhances the anti-tumor sensitivity of rapamycin.