Predicting the treatment effect of sorafenib using new biomarker in patients with hepatocellular carcinoma

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19372
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Kansai Medical University
• Principal Investigator: YAMAGUCHI Takashi 関西医科大学, 医学部, 助教 (10730202)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 肝細胞癌 / ソラフェニブ / TGF-beta / Smad / 循環癌細胞

Outline of Final Research Achievements

Sorafenib inhibits the proliferation by switching the phospho-Smad3 signaling from the carcinogenic pSmad3L pathway to the tumor-suppressive pSmad3C pathway in hepatocellular carcinoma (HCC) cell lines. To isolate circulating tumor cells (CTC) from peripheral boood, immunomagnetis methods using autoMACS Pro Separator with anti-EpCAM antibodies specific to epitherial antigens and anti-CD45 antibodies used for negative selection of leucocytes in combination with immunocytochemistry with anti-pSmad3L antibodies were established. The whole blood, treated using this strategy, obtained from patients with HCC before sorafenib treatment. However, no CTC obtained from any patients. Thus, this strategy should be improved to detect CTC. The interest in development of domain specific phospho-Smad antibodies should lead to more sensitive and specific detection of CTC in the future.

Free Research Field

肝臓学

Academic Significance and Societal Importance of the Research Achievements

切除不能な進行肝細胞癌の第一選択薬であるソラフェニブは、その治療効果が個々の患者によって大きく異なるため、早期の治療効果判定が必要であるが、実臨床では画像診断に頼らざるを得ないため、リアルタイムでの効果判定は不可能である。本研究では、進行肝細胞癌に対するソラフェニブ治療のリアルタイムな治療効果判定を可能にするバイオマーカーの開発を行った。リン酸化Smadシグナルの解析はソラフェニブの効果をリアルタイムで反映するため、有用なバイオマーカーとなる可能性がある。