Personalised treatment of advanced hepatocellular carcinoma using circulating tumor DNA

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08352
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Tateishi Ryosuke 東京大学, 医学部附属病院, 准教授 (50444089)
• Co-Investigator(Kenkyū-buntansha): 中川 勇人 東京大学, 医学部附属病院, 届出研究員 (00555609) ; 田中 康雄 東京大学, 医学部附属病院, 届出研究員 (40422290) ; 中塚 拓馬 東京大学, 医学部附属病院, 助教 (50772042)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: cell free DNA / 循環腫瘍DNA / リキッドバイオプシー / 肝細胞癌

Outline of Final Research Achievements

This study aimed to assess the clinical utility of cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) in hepatocellular carcinoma. The results indicated a positive association between cfDNA levels and hepatocellular carcinoma progression, acting as an independent prognostic factor for poor outcomes. Notably, cfDNA levels exhibited a significant increase a few days following the initiation of pharmacological treatment, and a greater elevation corresponded to a higher likelihood of treatment success. Furthermore, analysis of post-treatment plasma revealed the presence of abundant ctDNA derived from disintegrating tumors, particularly several days after treatment. In lenvatinib-responsive patients, targeted ultra-deep sequencing of post-treatment plasma demonstrated promising potential for detecting gene mutations involved in therapeutic response to drug therapy.

Free Research Field

消化器内科　肝臓病学

Academic Significance and Societal Importance of the Research Achievements

進行肝癌に対する薬物治療は近年大きく進歩したが、治療奏功性を事前に推測する方法はまだ確立していない。本研究の成果により、cell-free DNAの量的変化によって治療奏功性を予測できる可能性や、血中循環腫瘍由来DNAを用いた網羅的遺伝子変異解析により治療奏功性に関与する遺伝子変異を探索できる可能性が示唆された。肝癌に対するゲノム医療、個別化医療の発展が必要とされる中で、重要な知見が得られたと考える。