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Personalised treatment of advanced hepatocellular carcinoma using circulating tumor DNA

Research Project

Project/Area Number 20K08352
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionThe 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
Project Status Completed (Fiscal Year 2022)
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)
Keywordscell 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
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。

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.

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。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (20 results)

All 2023 2022 2021 2020

All Journal Article (13 results) (of which Peer Reviewed: 13 results,  Open Access: 3 results) Presentation (7 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Development and prognosis of hepatocellular carcinoma in patients with diabetes2023

    • Author(s)
      Nakatsuka Takuma、Tateishi Ryosuke
    • Journal Title

      Clinical and Molecular Hepatology

      Volume: 29 Issue: 1 Pages: 51-64

    • DOI

      10.3350/cmh.2022.0095

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Agile scores are a good predictor of liver-related events in patients with NAFLD2023

    • Author(s)
      Nakatsuka Takuma、Tateishi Ryosuke、Sato Masaya、Fujishiro Mitsuhiro、Koike Kazuhiko
    • Journal Title

      Journal of Hepatology

      Volume: - Issue: 3 Pages: e126-e127

    • DOI

      10.1016/j.jhep.2023.02.029

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Risk stratification of hepatocellular carcinoma after hepatitis C virus eradication in patients with compensated advanced chronic liver disease in Japan2022

    • Author(s)
      Nakatsuka Takuma、Tateishi Ryosuke、Nakagomi Ryo、Minami Tatsuya、Koike Kazuhiko
    • Journal Title

      Journal of Hepatology

      Volume: 3 Issue: 2 Pages: 138-138

    • DOI

      10.1016/j.jhep.2022.03.002

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impact of Obesity and Heavy Alcohol Consumption on Hepatocellular Carcinoma Development after HCV Eradication with Antivirals2021

    • Author(s)
      Minami Tatsuya、Tateishi Ryosuke、Nakatsuka Takuma、Nakagawa Hayato、et al.
    • Journal Title

      Liver Cancer

      Volume: 10 Issue: 4 Pages: 309

    • DOI

      10.1159/000513705

    • URL

      https://pure.teikyo.jp/en/publications/9501b6f6-f3aa-4d05-8db6-86c10b130078

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prognosis prediction or treatment allocation?2021

    • Author(s)
      Tateishi Ryosuke
    • Journal Title

      Hepatology International

      Volume: 15 Issue: 4 Pages: 852-854

    • DOI

      10.1007/s12072-021-10201-x

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Changing clinical management of NAFLD in Asia2021

    • Author(s)
      Nakatsuka Takuma、Tateishi Ryosuke、Koike Kazuhiko
    • Journal Title

      Liver International

      Volume: 8 Issue: 9 Pages: 15046-15046

    • DOI

      10.1111/liv.15046

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Limited efficacy of atezolizumab and bevacizumab for hepatocellular carcinoma previously treated with tyrosine kinase inhibitor2021

    • Author(s)
      Yamada Tomoharu、Minami Tatsuya、Tateishi Ryosuke、Koike Kazuhiko
    • Journal Title

      Liver International

      Volume: 41 Issue: 9 Pages: 2233-2234

    • DOI

      10.1111/liv.15010

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Infectious complications related to radiofrequency ablation of liver tumors: The role of antibiotics2021

    • Author(s)
      Nakagomi Ryo、Tateishi Ryosuke、Mikami Shintaro、Wake Taijiro、Kinoshita Mizuki Nishibatake、Nakatsuka Takuma、Minami Tatsuya、Sato Masaya、Uchino Koji、Enooku Kenichiro、Nakagawa Hayato、Asaoka Yoshinari、Shiina Shuichiro、Koike Kazuhiko
    • Journal Title

      PLOS ONE

      Volume: 16 Issue: 11 November Pages: 0259641-0259641

    • DOI

      10.1371/journal.pone.0259641

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Post-treatment cell-free DNA as a predictive biomarker in molecular-targeted therapy of hepatocellular carcinoma2021

    • Author(s)
      Nakatsuka T、Nakagawa H、Hayata Y、Wake T、Yamada T、Nishibatake Kinoshita M、Nakagmi R、Sato M、Minami T、Uchino K、Enooku K、Kudo Y、Tanaka Y、Kishikawa T、Otsuka M、Tateishi R、Koike K
    • Journal Title

      Journal of Gastroenterology

      Volume: - Issue: 5 Pages: 01773-4

    • DOI

      10.1007/s00535-021-01773-4

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Radiofrequency Ablation of Liver Tumors in Patients on Antithrombotic Therapy: A Case-Control Analysis of over 10,000 Treatments2021

    • Author(s)
      Uchino Koji、Tateishi Ryosuke、Wake Taijiro、Kinoshita Mizuki Nishibatake、Nakagomi Ryo、Nakatsuka Takuma、Minami Tatsuya、Sato Masaya、Enooku Kenichiro、Nakagawa Hayato、Shiina Shuichiro、Koike Kazuhiko
    • Journal Title

      Journal of Vascular and Interventional Radiology

      Volume: - Issue: 6 Pages: 869-877

    • DOI

      10.1016/j.jvir.2021.02.021

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hepatocellular carcinoma development in diabetic patients: a nationwide survey in Japan2021

    • Author(s)
      Tateishi R、Matsumura T、Okanoue T、Shima T、Uchino K、Fujiwara N、Senokuchi T、Kon K、Sasako T、Taniai M、Kawaguchi T、Inoue H、Watada H、Kubota N、Shimano H、Kaneko S、Hashimoto E、Watanabe S、Shiota G、Ueki K、Kashiwabara K、Matsuyama Y、Tanaka H、Kasuga M、Araki E、Koike K
    • Journal Title

      Journal of Gastroenterology

      Volume: 56 Issue: 3 Pages: 261

    • DOI

      10.1007/s00535-020-01754-z

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neoadjuvant use of oncolytic herpes virus G47Δ enhances the antitumor efficacy of radiofrequency ablation.2020

    • Author(s)
      Yamada T, Tateishi R, Iwai M, Koike K, Todo T
    • Journal Title

      Mol Ther Oncolytics

      Volume: 18 Pages: 535-545

    • DOI

      10.1016/j.omto.2020.08.010

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Improved liver function in patients with cirrhosis due to chronic hepatitis C virus who achieve sustained virologic response is not accompanied by increased liver volume2020

    • Author(s)
      Wake Taijiro、Tateishi Ryosuke、Fukumoto Tsuyoshi、Nakagomi Ryo、Kinoshita Mizuki Nishibatake、Nakatsuka Takuma、Sato Masaya、Minami Tatsuya、Uchino Koji、Enooku Kenichiro、Nakagawa Hayato、Fujinaga Hidetaka、Asaoka Yoshinari、Tanaka Yasuo、Otsuka Motoyuki、Koike Kazuhiko
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 4 Pages: e0231836-e0231836

    • DOI

      10.1371/journal.pone.0231836

    • URL

      https://pure.teikyo.jp/en/publications/fc54350e-ae3f-49ea-8e39-98b85bff7a2e

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ラジオ波焼灼術後の腫瘍検体と血漿を用いた肝癌ゲノム解析の可能性2022

    • Author(s)
      中塚拓馬、中川勇人、森山慎、福本剛、山田友春、和気泰次郎、佐藤雅哉、南達也、工藤洋太郎、建石良介
    • Organizer
      第1回 日本アブレーション研究会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 肝癌におけるラジオ波焼灼後腫瘍生検の臨床的有用性および遺伝子変異解析の可能性2022

    • Author(s)
      中塚拓馬、内野康志、中川勇人、森山慎、福本剛、山田友春、和気泰次郎、佐藤雅哉、南達也、工藤洋太郎、建石良介、藤城光弘
    • Organizer
      第58回日本肝癌研究会
    • Related Report
      2022 Annual Research Report
  • [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
      2021 Research-status Report
    • Int'l Joint Research
  • [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
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Circulating tumor DNA 解析による肝癌層別化治療に向けた試み2020

    • Author(s)
      中塚拓馬、中川勇人、小池和彦
    • Organizer
      第56回肝臓学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 治療後cell-free DNA解析による肝癌ゲノム医療に向けた試み2020

    • Author(s)
      中塚拓馬、中川勇人、小池和彦
    • Organizer
      第28回日本消化器関連学会週間(JDDW 2020)
    • Related Report
      2020 Research-status Report
  • [Presentation] 治療後 cell-free DNA 解析による分子標的薬の治療効果予測2020

    • Author(s)
      中塚拓馬、中川勇人、早田有希、和気泰次郎、山田友春、木下瑞希、中込良、 佐藤雅哉、南達也、榎奥健一郎、工藤洋太郎、田中康雄、大塚基之、建石良介、小池和彦
    • Organizer
      第23回日本肝がん分子標的治療研究会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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