Personalised treatment of advanced hepatocellular carcinoma using circulating tumor DNA
| Project/Area Number |
20K08352
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| 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)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | cell free DNA / 循環腫瘍DNA / リキッドバイオプシー / 肝細胞癌 / 血中循環腫瘍DNA / ゲノム医療 / バイオマーカー / ゲノム異常 / 個別化医療 |
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| Outline of Research at the Start |
本研究では血液内を循環している腫瘍DNA（circulating tumor DNA, ctDNA）を肝癌の局所治療・動脈塞栓術・分子標的薬などの治療を受けた患者から採取し、そのゲノム異常を統合的に解析する。さらに患者の臨床データと比較することで、ctDNAを用いた肝癌の早期診断や再発予測、治療モニタリング、治療効果の予測アルゴリズムの構築を試みる。
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| 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.
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| 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。
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Report
(4 results)
Research Products
(20 results)
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[Presentation] Post-treatment cell-free DNA as a predictive biomarker in molecular-targeted therapy of hepatocellular carcinoma2021
Author(s)
Takuma Nakatsuka, Hayato Nakagawa, Yuki Hayata, Taijiro Wake, Tomoharu Yamada, Ryo Nakagomi, Masaya Sato, Tatsuya Minami, Koji Uchino, Kenichiro Enooku, Yotaro Kudo, Yasuo Tanaka, Motoyuki Otsuka, Ryosuke Tateishi, Kazuhiko Koike
Organizer
JSH International Liver Conference 2021
Related Report
Int'l Joint Research
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[Presentation] Post-treatment cell-free DNA as a predictive biomarker in systemic therapy for HCC2021
Author(s)
Takuma Nakatsuka, Hayato Nakagawa, Taijiro Wake, Tomoharu Yamada, Masaya Sato, Tatsuya Minami, Yotaro Kudo, Yasuo Tanaka, Motoyuki Otsuka, Ryosuke Tateishi, Kazuhiko Koike
Organizer
APASL Oncology 2021
Related Report
Int'l Joint Research
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