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Toward BNCT with Multi-Drug Boron Drugs

Research Project

Project/Area Number 21K09176
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56010:Neurosurgery-related
Research InstitutionOkayama University

Principal Investigator

Michiue Hiroyuki  岡山大学, 中性子医療研究センター, 准教授 (20572499)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsホウ素中性子捕捉療法 / 悪性脳腫瘍 / ホウ素薬剤 / 悪性腫瘍 / グルコース輸送体 / プレシジョンメディスン / 創薬研究 / 糖輸送体標的薬剤 / 抗がん剤
Outline of Research at the Start

BNCT(ホウ素中性子捕捉療法)は、標的となる悪性腫瘍細胞へホウ素薬剤を導入させ、同部位に中性子を照射し、ホウ素と中性子の核反応により腫瘍細胞を殺傷する細胞レベルのがん治療法である。しかし、現在臨床に使用可能なホウ素薬剤は、アミノ酸(フェニルアラニン)にホウ素を結合させたBPAのみである。我々の問いは、「ホウ素薬剤はBPAの1剤で充分か?」 である。今回、BNCTにおける治療の向上へ向け、ホウ素薬剤においても同理論が適応可能と考え、ホウ素薬剤の多剤併用を目標とした新規ホウ素薬剤の開発へ取り組む。

Outline of Final Research Achievements

The success of treatment in BNCT is highly dependent on the uptake of the drug into tumor tissue and tumor cells. The medically approved boron drug BPA exhibits tumor-accumulating properties via amino acid transporters (LAT-1). First, bioinformatics analysis of glucose transporters (GLUT1, GLUT3) in addition to LAT-1 was performed across cancers using TCGA. LAT-1 expression was high in malignant brain tumors, and GLUT1 and GLUT3 expression was high in pancreatic cancer with high CA19-9 levels. He has contributed to the efforts to expand the lineup of new drugs in addition to BPA in BNCT.

Academic Significance and Societal Importance of the Research Achievements

BNCTは、化学療法としてのホウ素薬剤、放射線治療としての中性子照射により構成される、化学放射線療法である。中性源が原子炉より病院設置可能な加速器中性子源へと移行し、医療化への実現性が進んでいる。2020年にBPAの薬事承認がされ、BNCT成功の鍵は今後のホウ素薬剤ラインナップの拡充に大きく依存する。がん高発現のグルコース輸送体を標的とした交換外材結合の薬剤開発はこれまだに多く報告されているが、未だ成功例は無い。今回、グルコース結合ホウ素薬剤を利用することで、グルコース結合薬剤の問題点である脳への中枢神経障害の回避に成功した。今後のBNCT発展に貢献する新たな研究成果である。

Report

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

    (15 results)

All 2023 2022 2021

All Journal Article (7 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (7 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Low frequency of intracranial progression in advanced NSCLC patients treated with cancer immunotherapies2023

    • Author(s)
      Kemmotsu N , Ninomiya K , Kunimasa K , IshinoT ,Nagasaki J , Otani Y , Michiue H ,Ichihara E ,Ohashi K ,Inoue T ,Tamiya M ,Sakai K ,Ueda Y , Dansako H ,Nishio K ,Kiura K , Date I ,Togashi Y
    • Journal Title

      International Journal of Cancer

      Volume: 154(1) Issue: 1 Pages: 169-179

    • DOI

      10.1002/ijc.34700

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ADAR1 is a promising risk stratification biomarker of remnant liver recurrence after hepatic metastasectomy for colorectal cancer2023

    • Author(s)
      Nanako Hata, Kunitoshi Shigeyasu, Sho Takeda, et al.
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 2078-2078

    • DOI

      10.1038/s41598-023-29397-z

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proposal of recommended experimental protocols for <i>in vitro</i> and <i>in vivo</i> evaluation methods of boron agents for neutron capture therapy2023

    • Author(s)
      Hattori Yoshihide、Andoh Tooru、Kawabata Shinji、Hu Naonori、Michiue Hiroyuki、Nakamura Hiroyuki、Nomoto Takahiro、Suzuki Minoru、Takata Takushi、Tanaka Hiroki、Watanabe Tsubasa、Ono Koji
    • Journal Title

      Journal of Radiation Research

      Volume: 64 Issue: 6 Pages: 859-869

    • DOI

      10.1093/jrr/rrad064

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] RNA Editing is a Valuable Biomarker for Predicting Carcinogenesis in Ulcerative Colitis2022

    • Author(s)
      Takahashi Kazutaka、Shigeyasu Kunitoshi、Kondo Yoshitaka、Gotoh Kazuyoshi、Yano Shuya、Umeda Yuzo、Inokuchi Toshihiro、Xu Caiming、Yoshida Kazuhiro、Umeda Hibiki、Takahashi Toshiaki、Takeda Sho、Yoshida Ryuichi、Teraishi Fuminori、Kishimoto Hiroyuki、Mori Yoshiko、Noma Kazuhiro、Okugawa Yoshinaga、et al.
    • Journal Title

      Journal of Crohn's and Colitis

      Volume: jjac186 Issue: 5 Pages: 754-766

    • DOI

      10.1093/ecco-jcc/jjac186

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Regulatory T cells induce a suppressive immune milieu and promote lymph node metastasis in intrahepatic cholangiocarcinoma2022

    • Author(s)
      Konishi DaisukeKishimoto Hiroyuki、Michiue Hiroyuki、Teraishi Fuminori、Kato Hironari、Tazawa Hiroshi、Yanai Hiroyuki、Yagi Takahito、Goel Ajay、Fujiwara Toshiyoshi
    • Journal Title

      British Journal of Cancer

      Volume: 127 Issue: 4 Pages: 757-765

    • DOI

      10.1038/s41416-022-01838-y

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] RNA editing facilitates the enhanced production of neoantigens during the simultaneous administration of oxaliplatin and radiotherapy in colorectal cancer2022

    • Author(s)
      Komatsu Yasuhiro、Shigeyasu Kunitoshi、Kagawa Shunsuke、Michiue Hiroyuki、Tazawa Hiroshi、Goel Ajay、Fujiwara Toshiyoshi
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 00-00

    • DOI

      10.1038/s41598-022-17773-0

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Combination of Ad-SGE-REIC and bevacizumab modulates glioma progression by suppressing tumor invasion and angiogenesis2022

    • Author(s)
      Hattori Yasuhiko、Kurozumi Kazuhiko、Otani Yoshihiro、Uneda Atsuhito、Tsuboi Nobushige、Makino Keigo、Hirano Shuichiro、Fujii Kentaro、Tomita Yusuke、Oka Tetsuo、Matsumoto Yuji、Shimazu Yosuke、Michiue Hiroyuki、Kumon Hiromi、Date Isao
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 8 Pages: 242-242

    • DOI

      10.1371/journal.pone.0273242

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Precision BNCT を目指した創薬戦略2023

    • Author(s)
      道上宏之
    • Organizer
      第7回 岡山大学中性子医療研究センターシンポジウム
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 腫瘍由来血管内皮細胞(TDEC)を標的とした 抗うつ薬による新規抗血管新生薬創薬2023

    • Author(s)
      道上宏之
    • Organizer
      第41回日本脳腫瘍学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] プレシジョンBNCTによる新たなホウ素薬剤創薬2023

    • Author(s)
      道上宏之
    • Organizer
      第19回日本中性子捕捉療法学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Precision BNCT strategies targeting incurable pancreatic cancer.2022

    • Author(s)
      道上宏之 藤本卓也 金平典之  寺石文則  井川和代 近藤夏子  櫻井良憲  鈴木実  藤原俊義
    • Organizer
      第18回日本中性子捕捉療法学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Precision BNCT へ向けたホウ素薬剤開発」2022

    • Author(s)
      道上宏之
    • Organizer
      岡山大学中性子医療研究センター第6回シンポジウム
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] BSH/ペプチドDDSによる新規ホウ素薬剤開発2021

    • Author(s)
      道上宏之
    • Organizer
      第17回日本中性子捕捉療法学会学術大会
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] ホウ素薬剤開発に基づく これからのBNCT戦略2021

    • Author(s)
      道上宏之
    • Organizer
      岡山大学中性子医療研究センターシンポジウム
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] 悪性腫瘍治療薬2021

    • Inventor(s)
      道上宏之
    • Industrial Property Rights Holder
      道上宏之
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-193305
    • Filing Date
      2021
    • Related Report
      2021 Research-status Report

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

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