Development of molecular diagnostic system for the prediction of therapeutic effect in liver cancer

2016 Fiscal Year Final Research Report

• Project/Area Number: 26670387
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Okuse Chiaki 聖マリアンナ医科大学, 医学部, 教授 (00318940)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 肝細胞癌 / Sorafenib / 治療効果予測 / DNAメチル化 / VEGFR / PDGFR / pyrosequencing

Outline of Final Research Achievements

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with poor prognosis. Sorafenib, an oral multikinase inhibitor, has been recognized as a new molecular-targeted therapy for HCC. Sorafenib suppresses tumor growth and angiogenesis by inhibiting the RAS/RAF/MAPK signaling pathway and tyrosine kinase receptors including vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor beta (PDGFRB). We analyzed DNA methylation of VEGFR and PDGFRB genes. We have detected DNA methylation of VEGFR and PDGFRB genes in a subset of HCC cell lines and tissues. We were also able to anakyze DNA methylation of these genes using circulating cell free DNA. DNA methylation of these genes may become a biomarker for the prediction of Sorafenib sensitivity in patients with HCC. Our results warrant further investigation.

Free Research Field

消化器内科学