Phosphorylated ERK is a potential prognostic biomarker for Sorafenib response in hepatocellular carcinoma

Abstract

Sorafenib, the only approved drug for hepatocellular carcinoma, acts as a remarkable inhibitor of Raf serine-threonine kinases. However, Sorafenib is expensive, and clinical experience shows that it is not an effective treatment for many patients. Previous study has demonstrated that phosphorylated ERK (pERK) is a key downstream component in the RAF/MEK/ERK signaling pathway. Here, we investigate whether pERK is a useful biomarker for treating HCC with Sorafenib. In vitro cell viability assays showed that the efficacy of Sorafenib was distinctly different according to the level of pERK. Furthermore, in established patient-derived xenografts from HCC specimens, we found that the growth rate of tumors with high levels of pERK was significantly decreased by Sorafenib treatment. Taken together, pERK is a potential biomarker for the sensitivity to Sorafenib in treating HCC.

In hepatocellular carcinoma (HCC), the efficacy of Sorafenib remains moderate and certain patients display a short period of survival following treatment. Our vitro and in vivo results revealed the relationship between the expression of phosphorylated ERK (pERK) and Sorafenib response in HCC. We confirmed that tumors containing higher levels of pERK are more sensitive to Sorafenib. pERK may be a useful biomarker in treating HCC with Sorafenib.

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