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

Yuelong Liang; Jiang Chen; Qingsong Yu; Tong Ji; Bin Zhang; Junjie Xu; Yi Dai; Yangyang Xie; Hui Lin; Xiao Liang; Xiujun Cai

doi:10.1002/cam4.1228

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

Cancer Med. 2017 Dec;6(12):2787-2795. doi: 10.1002/cam4.1228. Epub 2017 Oct 13.

Authors

Yuelong Liang¹, Jiang Chen¹, Qingsong Yu¹, Tong Ji¹, Bin Zhang¹, Junjie Xu¹, Yi Dai¹, Yangyang Xie¹, Hui Lin¹, Xiao Liang¹, Xiujun Cai¹

Affiliation

¹ Department of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310016, China.

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.

Keywords: Biomarkers; Hepatocellular carcinoma; Phosphorylated ERK; Sorafenib.

MeSH terms

Animals
Antineoplastic Agents / pharmacology*
Biomarkers, Tumor / metabolism*
Carcinoma, Hepatocellular / drug therapy*
Carcinoma, Hepatocellular / enzymology
Carcinoma, Hepatocellular / genetics
Carcinoma, Hepatocellular / pathology
Cell Proliferation / drug effects
Cell Survival / drug effects
Dose-Response Relationship, Drug
Extracellular Signal-Regulated MAP Kinases / metabolism*
Female
Gene Expression Regulation, Neoplastic
Hep G2 Cells
Histone-Lysine N-Methyltransferase / genetics
Histone-Lysine N-Methyltransferase / metabolism
Humans
Liver Neoplasms / drug therapy*
Liver Neoplasms / enzymology
Liver Neoplasms / genetics
Liver Neoplasms / pathology
Mice, Nude
Niacinamide / analogs & derivatives*
Niacinamide / pharmacology
Phenylurea Compounds / pharmacology*
Phosphorylation
Protein Kinase Inhibitors / pharmacology*
Sorafenib
Time Factors
Tumor Burden / drug effects
Xenograft Model Antitumor Assays

Substances

Antineoplastic Agents
Biomarkers, Tumor
Phenylurea Compounds
Protein Kinase Inhibitors
Niacinamide
Sorafenib
Histone-Lysine N-Methyltransferase
SETD7 protein, human
Extracellular Signal-Regulated MAP Kinases