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Therapy-induced rewiring of metabolism and elaboration of the adjuvant therapy in breast cancer.

Research Project

Project/Area Number 19K09109
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55010:General surgery and pediatric surgery-related
Research InstitutionMiyagi Prefectural Hospital Organization Miyagi Cancer Center

Principal Investigator

Kawai Masaaki  地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 共同研究員 (80513530)

Co-Investigator(Kenkyū-buntansha) 島 礼  地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 部長 (10196462)
角川 陽一郎  地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 特任研究員 (60221173)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords化学療法 / 細胞老化 / 代謝 / 乳がん / 放射線療法
Outline of Research at the Start

我々は最近、抗がん剤処理を受けた後に生存する残存腫瘍細胞における代謝酵素スイッチを見出だした。これまでの検討で、この代謝酵素スイッチは、DNA損傷への応答であることが示唆されている。重要なことに、このイベントが抗がん剤耐性に大きく寄与することも示唆されている。本研究では、化学/放射線療法に伴う代謝酵素スイッチの普遍性やメカニズム、意義の解明に取り組む。治療ストレス下の代謝応答を標的にした乳がん補助療法の錬成に向けて、その基礎となるデータを収集する。

Outline of Final Research Achievements

The concept that improving therapeutic outcomes by eliminating or suppressing the activity of senescent tumor cells induced by chemotherapy and radiotherapy was investigated. In particular, we focused on the enhanced NAD synthesis in therapy-induced cellular senescence. In a xenografts model in mice, cisplatin chemotherapy and small-molecule inhibitor of NAD synthesis showed highly synergistic therapeutic effects. We also examined whether NAD metabolism could be interfered with by restricting the dietary NAD precursors. The effects of such dietary intervention on the composition of various nutrients in blood were comprehensively examined in animal models.

Academic Significance and Societal Importance of the Research Achievements

マウスxenograftでの治療実験におけるシスプラチン・NAD合成阻害の高い相乗効果は、今後さらなる検証をすすめる価値がある。また、今回はシスプラチンのみでの検討だが、他抗ガン剤や放射線治療とNAD合成阻害の併用についても検討する意義は高い。一方、米国を中心にプレシジョン(精密な)栄養学の概念が発達しつつある。そのような先進的概念を乳がん治療においても早期に取り入れるべきで、本研究はその一歩とみることが可能だろう。食事改変により化学療法の成績が変わったという今回の結果は、一層の検証を行う価値があると思われる。

Report

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

    (5 results)

All 2022 2021 2020

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 3 results)

  • [Journal Article] Bird's eye view analysis of in situ cholesterol metabolic pathways in breast cancer patients and its clinicopathological significance in their subtypes.2022

    • Author(s)
      Kosaka S, Miyashita M, McNamala K, Nomura M, Shima H, Kawai M, Sato I, Harada-Shoji N, Ishida T, Choi MH, Sasano H
    • Journal Title

      J Steroid Biochem Mol Biol

      Volume: 印刷中 Pages: 106103-106103

    • DOI

      10.1016/j.jsbmb.2022.106103

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Targeting Amino Acid Metabolic Reprogramming via L-Type Amino Acid Transporter 1 (LAT1) for Endocrine-Resistant Breast Cancer2021

    • Author(s)
      Shindo Haruhiko、Harada-Shoji Narumi、Ebata Akiko、Sato Miku、Soga Tomoyoshi、Miyashita Minoru、Tada Hiroshi、Kawai Masaaki、Kosaka Shinkichi、Onuki Koji、Usami Shin、Furumoto Shozo、Hayashi Shinichi、Abe Takaaki、Suzuki Takashi、Ishida Takanori、Sasano Hironobu
    • Journal Title

      Cancers

      Volume: 13 Issue: 17 Pages: 4375-4375

    • DOI

      10.3390/cancers13174375

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ppp6c deficiency accelerates K-rasG12D -induced tongue carcinogenesis.2021

    • Author(s)
      Kishimoto K, Kanazawa K, Nomura M, Tanaka T, Shigemoto-Kuroda T, Fukui K, Miura K, Kurosawa K, Kawai M, Kato H, Terasaki K, Sakamoto Y, Yamashita Y, Sato I, Tanuma N, Tamai K, Kitabayashi I, Matsuura K, Watanabe T, Yasuda J, Tsuji H, Shima H.
    • Journal Title

      Cancer Med.

      Volume: 10(13) Issue: 13 Pages: 4451-4464

    • DOI

      10.1002/cam4.3962

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Breast cancer survival among Japanese individuals and US residents of Japanese and other origins: a comparative registry-based study2020

    • Author(s)
      1.Ogiya R, Niikura N, Kumamaru H, Takeuchi Y, Okamura T, Kinoshita T, Aogi K, Anan K, Iijima K, Ishida T, Iwamoto T, Kawai M, Kojima Y, Sakatani T, Sagara Y, Hayashi N, Masuoka H, Yoshida M, Miyata H, Tsuda H, Imoto S, Jinno H.
    • Journal Title

      Breast cancer research and treatment

      Volume: 184 Issue: 2 Pages: 585

    • DOI

      10.1007/s10549-020-05869-y

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Divergent metabolic responses dictate vulnerability to NAMPT inhibition in ovarian cancer2020

    • Author(s)
      Kudo Kei、Nomura Miyuki、Sakamoto Yoshimi、Ito Shigemi、Morita Mami、Kawai Masaaki、Yamashita Yoji、Ito Kiyoshi、Yamada Hidekazu、Shima Hiroshi、Yaegashi Nobuo、Tanuma Nobuhiro
    • Journal Title

      FEBS Letters

      Volume: 594 Issue: 9 Pages: 1379-1388

    • DOI

      10.1002/1873-3468.13736

    • Related Report
      2020 Research-status Report
    • Peer Reviewed

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Published: 2019-04-18   Modified: 2023-01-30  

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