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Efficacy of molecular targeting therapy and establishment of patient derived model in ARID1A-deficient ovarian clear cell carcinoma

Research Project

Project/Area Number 17K11310
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionNational Cancer Center Japan

Principal Investigator

Tomoyasu Katoh  国立研究開発法人国立がん研究センター, 中央病院, 科長 (50224522)

Co-Investigator(Kenkyū-buntansha) 荻原 秀明  国立研究開発法人国立がん研究センター, 研究所, 分野長 (40568953)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords卵巣明細胞がん / 婦人科腫瘍 / 卵巣がん / ARID1A / 精密医療 / 合成致死 / SLC7A11 / グルタチオン / クロマチンリモデリング / 患者由来細胞株 / 最適化がん治療 / APR-246 / BSO / 分子標的治療 / OCCC / PDX
Outline of Final Research Achievements

Ovarian clear cell caricinoma is refractory cancer. Previously, we found the hopeful drug APR-246 for ARID1A-deficient cancers. In this study, we aim to develop the patient-derived models and investigate the promising of APR-246 for ARID1A-deficient cancers. We revealed that ARID1A deficiency caused decrease of SLC7A11 expression and APR-246 treatment suppressed cells and tumors growth in patient-derived models.

Academic Significance and Societal Importance of the Research Achievements

卵巣明細胞がんは、化学療法の効きにくい難治性がんのため新しい治療薬の開発が求められていた。本研究では、ARID1A欠損がんに有望な新規薬剤が卵巣明細胞がんの半数の患者に対して有望であることを示した。APR-246は臨床試験薬であり、今後ARID1A欠損がんへの有効性を検証することで卵巣明細胞がん患者に対する新規薬剤として臨床応用されることが期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (7 results)

All 2019 2018 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (2 results)

  • [Journal Article] Targeting the Vulnerability of Glutathione Metabolism in ARID1A-Deficient Cancers.2019

    • Author(s)
      Ogiwara H, Takahashi K, Sasaki M, Kuroda T, Yoshida H, Watanabe R, Maruyama A, Makinoshima H, Chiwaki F, Sasaki H, Kato T, Okamoto A, Kohno T.
    • Journal Title

      Cancer Cell

      Volume: 35 Issue: 2 Pages: 177-190

    • DOI

      10.1016/j.ccell.2018.12.009

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Targeting the Vulnerability of Glutathione Metabolism in ARID1A-Deficient Ovarian Clear Cell Carcinoma2019

    • Author(s)
      Kazuaki Takahashi1,2, Hideaki Ogiwara1, Mariko Sasaki1, Takafumi Kuroda1,2, Hiroshi Yoshida3, Reiko Watanabe3, Ami Maruyama4,5, Hideki Makinoshima4, Fumiko Chiwaki6, Hiroki Sasaki6, Tomoyasu Kato7, Aikou Okamoto2 and Takashi Kohno1
    • Organizer
      The 4th Asia-Pacific Ovarian Cancer Laparotomic and Laparoscopic Operation (APOLLO)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] SWI/SNFクロマチンリモデリング欠損がんにおける合成致死標的の探索2018

    • Author(s)
      Hideaki Ogiwara, Mariko Sasaki, Kazuaki Takahashi, Takafumi Kuroda, Takashi Kohno
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] クロマチンリモデリング複合体欠損がんにおける合成致死治療法の開発2018

    • Author(s)
      荻原秀明、佐々木麻里子、河野隆志
    • Organizer
      2018年第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Identification of Synthetic Lethal Targets in ARID1A-Deficient Ovarian Cancers2018

    • Author(s)
      Kazuaki Takahashi, Hideaki Ogiwara, Mariko Sasaki, Takafumi Kuroda, Reiko Watanabe, Hiroshi Yoshida, Tomoyasu Kato, Aikou Okamoto and Takashi Kohno
    • Organizer
      IGCS 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Remarks] 代謝(メタボローム)を標的とした新たながん治療法を発見

    • URL

      https://www.ncc.go.jp/jp/information/pr_release/2019/20190125/index.html

    • Related Report
      2018 Research-status Report
  • [Remarks] 最適化がん治療の研究

    • URL

      https://www.ncc.go.jp/jp/ri/division/genome_biology/project/020/20190125.html

    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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