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Assessment of Glycolysis/OXPHOS as ATP related cancer metabolism and overcoming of drug resistance in lung adenocarcinoma

Research Project

Project/Area Number 19K21338
Project/Area Number (Other) 18H06242 (2018)
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund (2019)
Single-year Grants (2018)
Review Section 0905:Surgery of the organs maintaining homeostasis and related fields
Research InstitutionHiroshima University

Principal Investigator

Mimae Takahiro  広島大学, 病院(医), 助教 (00634081)

Project Period (FY) 2018-08-24 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords肺腺癌 / がん代謝 / 酸化的リン酸化 / Glycolysis / ATP / 肺癌 / 薬剤耐性
Outline of Research at the Start

肺癌における全身化学療法は至適治療法選択やがん細胞の耐性獲得が問題になる。耐性獲得時に変化する代表的がん代謝として細胞エネルギーであるATP産生関連の経路が注目されている。これはAerobic glycolysis が優位なGlycolysis型とミトコンドリア内のTCA回路-ミトコンドリア呼吸が優位なOXPHOS型の大きく2つに分けられる。そこでその代謝経路に注目して、肺腺癌において 1、RNAシークエンスを用いた代謝分類(Glycolysis/OXPHOS型)2、化学療法前後における代謝変化を評価 3、優位代謝を標的とした治療薬および既存化学療法との併用の可能性検討 以上を目指す。

Outline of Final Research Achievements

To identify the novel target and development for therapy of lung adenocarcinoma, we identified the several pathways of dominant cancer metabolisms of lung adenocarcinoma and disclose that inhibitor targeting that cancer metabolism repressed the cell growth of lung adenocarcinoma in vitro. To investigate if the inhibitor is also effective in human, we examined TCGA (The Cancer Genome Atlas) database and found that human lung adenocarcinomas were classified based on the dominant cancer metabolism types. In addition, we are now trying to conduct human lung adenocarcinoma samples to immunohistochemistry targeting the representative molecules of the identified cancer metabolism. That results will provide useful information continuing to clinical application.

Academic Significance and Societal Importance of the Research Achievements

肺癌は未だ克服されていない病気であり、肺腺癌はその代表的な組織型の1つである。
本研究の結果は、その新規治療標的の同定および新規治療開発に関してがん代謝が非常に有望であることに加えて、実際に使用可能な拮抗薬の同定、ヒトへの応用の可能性の示唆にも至っている。動物実験や第1相臨床試験を経る必要はあるが、今後の臨床応用が期待される。また、がん代謝を標的とした治療はまだまだ確立されたものがないため新規性もある。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • Research Products

    (3 results)

All 2020 2019

All Journal Article (3 results) (of which Peer Reviewed: 3 results)

  • [Journal Article] Are segmentectomy and lobectomy comparable in terms of curative intent for early stage non-small cell lung cancer?2020

    • Author(s)
      Mimae T, Okada M.
    • Journal Title

      Gen Thorac Cardiovasc Surg.

      Volume: online ahead of print Issue: 7 Pages: 703-706

    • DOI

      10.1007/s11748-019-01219-y

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Solid Tumor Size of 2 cm Divides Outcomes of Patients With Mixed Ground Glass Opacity Lung Tumors.2020

    • Author(s)
      Mimae T, Tsutani Y, Miyata Y, Imai K, Ito H, Nakayama H, Ikeda N, Okada M.
    • Journal Title

      Ann Thorac Surg.

      Volume: in press Issue: 5 Pages: 1530-1536

    • DOI

      10.1016/j.athoracsur.2019.12.008

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Guanylate binding protein 1 (GBP-1) promotes cell motility and invasiveness of lung adenocarcinoma.2019

    • Author(s)
      Yamakita I, Mimae T, Tsutani Y, Miyata Y, Ito A, Okada M
    • Journal Title

      Biochemical and biophysical research communications

      Volume: 518 Issue: 2 Pages: 266-272

    • DOI

      10.1016/j.bbrc.2019.08.045

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed

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Published: 2018-08-27   Modified: 2024-03-26  

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