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Molecular gene signature and molecular targeted therapy for pancreatic cancer

Research Project

Project/Area Number 21K08757
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionKumamoto University

Principal Investigator

Nakagawa Shigeki  熊本大学, 病院, 特任助教 (10594872)

Co-Investigator(Kenkyū-buntansha) 馬場 秀夫  熊本大学, 大学院生命科学研究部(医), 教授 (20240905)
山下 洋市  熊本大学, 大学院生命科学研究部(医), 准教授 (00404070)
今井 克憲  熊本大学, 大学院生命科学研究部(医), 特定研究員 (60555746)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords膵癌 / Molecular gene signature / 予後 / バイオマーカー / Cofilin-1 / ARHGEF2 / 化学療法 / ARDHGEF2 / 治療標的 / gene signature
Outline of Research at the Start

膵癌は癌の中でも極めて予後が悪いことが知られている。世界的に見ても膵癌は死亡者数の上位を占めており、予防や早期診断、治療法、再発予防の開発は急務であると言える。このため、再発高リスク群を同定するマーカーの開発や、それに対して有効な分子標的薬の開発が急務である。
今回我々は、網羅的な遺伝子データベースに基づいて
①再発ハイリスク群を同定するバイオマーカーを作成すること
②網羅的な遺伝子解析を用いて再発ハイリスク群に対して効果的な治療標的を検討すること
③候補となる治療標的遺伝子の作用機序の解明及びヒト検体を用いた効果の検証すること
を目的とした。

Outline of Final Research Achievements

Pancreatic ductal adenocarcinoma had a worthy prognosis and there are a fewer chemotherapy regimens for pancreatic cancer. We tried to find the molecular gene signature predictive worth prognosis for pancreatic cancer patients and search the target genes for molecular targeted therapy.
We find CFL1 and ARHGEF2 as a targetable genes and analyze their effect for pancreatic cancer.

Academic Significance and Societal Importance of the Research Achievements

本研究においては、① 再発ハイリスク群を同定するバイオマーカーを作成し検証すること、② 網羅的な遺伝子解析を用いて再発ハイリスク群に対して効果的な治療標的を検討すること(Cofilin-1、ARDHGEF2)、③ Cofilin-1及びARDHGEF2の作用機序の解明及びヒト検体を用いた効果の検証することを目的とする。本研究における治療標的の検索方法やヒト検体を用いたCofilin-1及びARDHGEF2阻害剤の効果検証の方法等は網羅的、かつ非侵襲的にヒト検体における効果を検証する事が可能であり、極めて新規性・有効性が高いものと考えられる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (8 results)

All 2024 2023 2022 2021

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] RAS mutation status in combination with the JSHBPS nomogram may be useful for preoperative identification of colorectal liver metastases with high risk of recurrence and mortality after hepatectomy.2024

    • Author(s)
      Toru Takematsu
    • Journal Title

      J Hepatobiliary Pancreat Sci.

      Volume: 31 (2) Issue: 2 Pages: 69-79

    • DOI

      10.1002/jhbp.1389

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Disseminative Recurrence Signature for Hepatocellular Carcinoma From Nonalcoholic Fatty Liver Disease.2023

    • Author(s)
      Naoto Fujiwara
    • Journal Title

      Gastro Hep Adv.

      Volume: 2(5) Issue: 5 Pages: 681-683

    • DOI

      10.1016/j.gastha.2023.03.021

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Prognostic Role of Serine Racemase in Patients With Pancreatic Cancer: A New Marker in Cancer Metabolism2023

    • Author(s)
      Chuan Lan
    • Journal Title

      Pancreas .

      Volume: 52(2) Issue: 2 Pages: e101-e109

    • DOI

      10.1097/mpa.0000000000002210

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Statins exert anti-growth effects by suppressing YAP/TAZ expressions via JNK signal activation and eliminate the immune suppression by downregulating PD-L1 expression in pancreatic cancer2023

    • Author(s)
      Norio Uemura
    • Journal Title

      Am J Cancer Res .

      Volume: 13(5) Pages: 2041-2054

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hyperglycaemia induces metabolic reprogramming into a glycolytic phenotype and promotes epithelial-mesenchymal transitions via YAP/TAZ-Hedgehog signalling axis in pancreatic cancer.2023

    • Author(s)
      Liu Z,
    • Journal Title

      Br J Cancer.

      Volume: 128(5) Issue: 5 Pages: 844-856

    • DOI

      10.1038/s41416-022-02106-9

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] High Expression of Bloom Syndrome Helicase is a Key Factor for Poor Prognosis and Advanced Malignancy in Patients with Pancreatic Cancer: A Retrospective Study.2022

    • Author(s)
      Lan C
    • Journal Title

      Ann Surg Oncol.

      Volume: 29(6) Pages: 3551-3564

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] High ARHGEF2 (GEF-H1) Expression is Associated with Poor Prognosis Via Cell Cycle Regulation in Patients with Pancreatic Cancer2021

    • Author(s)
      Nakao Yosuke、Nakagawa Shigeki、Yamashita Yo-ichi、Umezaki Naoki、Okamoto Yuya、Ogata Yoko、Yasuda-Yoshihara Noriko、Itoyama Rumi、Yusa Toshihiko、Yamashita Kohei、Miyata Tatsunori、Okabe Hirohisa、Hayashi Hiromitsu、Imai Katsunori、Baba Hideo
    • Journal Title

      Annals of Surgical Oncology

      Volume: - Issue: 8 Pages: 4733-4743

    • DOI

      10.1245/s10434-020-09383-9

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] Hyperglycemia induces metabolic reprogramming and promotes epithelial-mesenchymal transitions in pancreatic cancer: An in vitro and in vivo experiment2023

    • Author(s)
      Zhao Liu
    • Organizer
      AACR Annual Meeting 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research

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Published: 2021-04-28   Modified: 2025-01-30  

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