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Search for Novel Cancer Therapeutic Targets Based on Large-Scale Genomics and Functional Screening

Research Project

Project/Area Number 22K16323
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionKyushu University

Principal Investigator

Hirabayashi Shigeki  九州大学, 医学研究院, 助教 (30910947)

Project Period (FY) 2022-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsがん / 血液腫瘍 / CRISPRスクリーニング
Outline of Research at the Start

近年のゲノム解析の進展により、血液腫瘍・がんの発症・維持に関与する遺伝子異常が複数同定され、それらに対する分子標的薬が開発されてきた。しかし、腫瘍に多様なクローンが存在するために、一部のクローンを分子標的薬で駆逐しても治療抵抗性の他のクローンが増殖し、根治がしばしば困難である。それゆえ、今なお従来の化学療法が欠かせないものとなっている。したがって、本研究ではがん細胞と正常細胞の生存に必須な遺伝子を同定することで、重篤な有害事象を抑えながらも血液腫瘍を主とした多彩ながんに奏功する新規治療法の開発を目指す。

Outline of Final Research Achievements

In recent years, molecular targeted drugs have been developed for hematologic tumors and cancers. However, even with treatment using molecular targeted drugs, resistant cells often proliferate, making complete eradication difficult. Therefore, this study aims to develop new therapies that are effective against a wide range of cancers while minimizing severe adverse events by identifying genes essential for the survival of both cancer and normal cells. First, 907 genes crucial for cancer survival were identified from cancer databases. Additionally, screening in hematopoietic stem cells identified 49 genes essential for cancer survival but not for hematopoietic stem cell survival, along with 11 disadvantageous genes. In the future, I hope to identify promising therapeutic targets from the identified genes.

Academic Significance and Societal Importance of the Research Achievements

日本における死因の第一は悪性新生物、つまりがんである。したがって、がんの治療に貢献する研究は社会的な意義が大きい。本研究成果はがんの生存に必須な遺伝子と正常な造血幹細胞に必須ではない遺伝子を同定することで、がん細胞特異的な治療を目指すもので、本研究の成果は今後の治療困難な広範な種類のがんの治療につながる可能性を秘めている。

Report

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

    (13 results)

All 2024 2023 2022

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 1 results) Presentation (6 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Central role of the mTORC1 pathway in glucocorticoid activity against B-ALL cells2024

    • Author(s)
      Imanaga H, Semba Y, Sasaki K, Setoguchi K, Maniriho H, Yamauchi T, Terasaki T, Hirabayashi S, Nakao F, Nogami J, Izraeli S, Akashi K, Maeda T
    • Journal Title

      Blood Neoplasia

      Volume: -

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Impact of MRD on clinical outcomes of unrelated hematopoietic stem cell transplantation in patients with Ph+ ALL: A retrospective nationwide study2023

    • Author(s)
      Hirabayashi S, Kondo T, Nishiwaki S, Mizuta S, Doki N, Fukuda T, Uchida N, Ozawa Y, Kanda Y, Imanaka R, Takahashi S, Ishikawa J, Yano S, Nakamae H, Eto T, Kimura T, Tanaka J, Ichinohe T, Atsuta Y, Kako S.
    • Journal Title

      American Journal of Hematology

      Volume: 98 Issue: 10 Pages: 1606-1618

    • DOI

      10.1002/ajh.27041

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Targeting a mitochondrial E3 ubiquitin ligase complex to overcome AML cell-intrinsic Venetoclax resistance2023

    • Author(s)
      Nakao Fumihiko、Setoguchi Kiyoko、Semba Yuichiro、Yamauchi Takuji、Nogami Jumpei、Sasaki Kensuke、Imanaga Hiroshi、Terasaki Tatsuya、Miyazaki Manaka、Hirabayashi Shigeki、Miyawaki Kohta、Kikushige Yoshikane、Masuda Takeshi、Akashi Koichi、Maeda Takahiro
    • Journal Title

      Leukemia

      Volume: - Issue: 5 Pages: 1028-1038

    • DOI

      10.1038/s41375-023-01879-z

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] HTLV-1 bZIP factor impairs DNA mismatch repair system2023

    • Author(s)
      Sakurada-Aono Maki、Sakamoto Takashi、Kobayashi Masayuki、Takiuchi Yoko、Iwai Fumie、Tada Kohei、Sasanuma Hiroyuki、Hirabayashi Shigeki、Murakawa Yasuhiro、Shirakawa Kotaro、Sakamoto Chihiro、Shindo Keisuke、Yasunaga Jun-ichirou、Matsuoka Masao、Pommier Yves、Takeda Shunichi、Takaori-Kondo Akifumi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 657 Pages: 43-49

    • DOI

      10.1016/j.bbrc.2023.03.049

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Advantages of peripheral blood stem cells from unrelated donors versus bone marrow transplants in outcomes of adult acute myeloid leukemia patients2022

    • Author(s)
      Jo Tomoyasu、Arai Yasuyuki、Kondo Tadakazu、Mizuno Shohei、Hirabayashi Shigeki et al.
    • Journal Title

      Cytotherapy

      Volume: 24 Issue: 10 Pages: 1013-1025

    • DOI

      10.1016/j.jcyt.2022.05.009

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of Multiple HLA Locus Mismatches on Outcomes after Single Cord Blood Transplantation.2022

    • Author(s)
      Kanda J, Hirabayashi S, Yokoyama H, Kawase T, Tanaka H, Uchida N, Taniguchi S, Takahashi S, Onizuka M, Tanaka M, Sugio Y, Eto T, Kanda Y, Kimura T, Ichinohe T, Atsuta Y, Morishima S.
    • Journal Title

      Transplant Cell Ther.

      Volume: 28 Issue: 7 Pages: 398-398

    • DOI

      10.1016/j.jtct.2022.05.005

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparing cord blood transplantation and matched related donor transplantation in non-remission acute myeloid leukemia2022

    • Author(s)
      Shimomura Y, Takahashi S., et al.
    • Journal Title

      Leukemia

      Volume: 36 Issue: 4 Pages: 1132-1138

    • DOI

      10.1038/s41375-021-01474-0

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Presentation] Genome-Wide CRISPR/Cas9 Screens Identify DDX19A/DDX19B As a Critical Regulator of Intrinsic Apoptosis By Regulating MCL1 mRNA Cellular Localization2023

    • Author(s)
      Terasaki T, Semba Y, Sasaki K, Miyata K, Yamauchi T, Imanaga H, Nakao F, Hirabayashi S, Nogami J, Akahane K, Inukai T, Akashi K, and Maeda T
    • Organizer
      65th ASH Annual Meeting
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification of Novel Transcripts and Potential Therapeutic Targets for Acute Leukemia2023

    • Author(s)
      Wada F, Kato S, Bhagat S, Hirabayashi S, Son R, Oguchi A, Takeuchi K, Sekito S, Hirai T, Zhang Z, Horisawa Y, Iwasaki M, Takeda J, Kanda J, Sakamoto T, Shirakawa K, Takaori-Kondo A, Murakawa Y
    • Organizer
      65th ASH Annual Meeting
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] GATOR1 complex is a critical regulator of glucocorticoid sensitivity in B-ALL cells2022

    • Author(s)
      今永博、仙波 雄一郎、佐々木謙介、宮田喜代子、山内拓司、寺崎達也、中尾文彦、平林茂樹、野上順平、赤司浩一、前田高宏
    • Organizer
      第84回日本血液学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] Mitochondrial E3 ligase complex regulates venetoclax sensitivity via modulating BAX equilibrium2022

    • Author(s)
      中尾文彦、仙波雄一郎、宮田喜代子、山内拓司、野上順平、今永博、寺崎達也、宮崎眞佳、平林茂樹、増田豪、赤司浩一、前田高宏
    • Organizer
      第84回日本血液学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] CRISPRスクリーンによりB-ALLにおけるグルココルチコイド感受性の制御因子としてGATOR1complexを同定2022

    • Author(s)
      今永博、平林茂樹、赤司浩一、前田高宏
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Research-status Report
  • [Presentation] A Genome-Wide CRISPR-Cas9 Screen Reveals GATOR1 Complex Is a Critical Regulator of Glucocorticoid Sensitivity in B-Cell Precursor Acute Lymphoblastic Leukemia2022

    • Author(s)
      Hiroshi Imanaga, Yuichiro Semba, Kensuke Sasaki, Kiyoko Miyata, Takuji Yamauchi, Tatsuya Terasaki, Fumihiko Nakao, Shigeki Hirabayashi et al.
    • Organizer
      64th ASH Annual Meeting
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research

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Published: 2022-04-19   Modified: 2025-01-30  

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