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Published on: May 26, 2017
Phosphorylated ERK is a potential prognostic biomarker for Sorafenib response in hepatocellular carcinoma
Yuelong Liang1, Jiang Chen1, Qingsong Yu1
1Department 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.
Insights
Phosphorylated ERK (pERK) may predict hepatocellular carcinoma (HCC) patient response to Sorafenib treatment. High pERK levels indicate potential sensitivity, offering a biomarker for personalized HCC therapy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Sorafenib is the sole approved drug for hepatocellular carcinoma (HCC), targeting Raf kinases.
- Its high cost and variable efficacy necessitate predictive biomarkers for patient selection.
- Phosphorylated ERK (pERK) is a critical downstream effector in the RAF/MEK/ERK pathway.
Purpose of the Study:
- To evaluate phosphorylated ERK (pERK) as a predictive biomarker for Sorafenib treatment efficacy in hepatocellular carcinoma (HCC).
Main Methods:
- In vitro cell viability assays were conducted to assess Sorafenib's effect based on pERK levels.
- Patient-derived HCC xenografts with varying pERK expression were used to evaluate tumor growth inhibition by Sorafenib.
Main Results:
- Sorafenib efficacy varied significantly in vitro depending on the baseline pERK expression.
- Sorafenib treatment markedly reduced tumor growth rates in patient-derived xenografts exhibiting high pERK levels.
Conclusions:
- Phosphorylated ERK (pERK) demonstrates potential as a predictive biomarker for Sorafenib sensitivity in HCC treatment.
- Identifying patients with high pERK could guide personalized therapeutic strategies for HCC.
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