Sorafenib-resistant hepatocellular carcinoma stratified by phosphorylated ERK activates PD-1 immune checkpoint.

ABSTRACT: Sorafenib is a multikinase inhibitor approved as the first line treatment for late stage hepatocellular carcinoma (HCC). Due to its significant variation in clinical benefits among patients, defining prognostic biomarkers for sorafenib sensitivity in HCC would allow targeted treatment. Phosphorylated extracellular signaling-regulated kinase (pERK) was proposed to predict the response to sorafenib in HCC, but clinical supports are mixed or even contradictory. Here we found that pERK expression levels are variable in different nodules from individual patient liver. Xenografts derived from resected tumors are resistant to sorafenib inhibition when expressing low levels of pERK. This correlation of low pERK levels and sorafenib resistance is corroborated by histological characterization of che

SUBMITTER: Chen J 

PROVIDER: S-EPMC5173058 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature