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Development of treatment for Lung Cancer with Fusion Proteins by inhibitors of polymerization in the coiled-coil domain

Research Project

Project/Area Number 18K08132
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionAsahikawa Medical College

Principal Investigator

SASAKI TAKAAKI  旭川医科大学, 医学部, 助教 (70516997)

Co-Investigator(Kenkyū-buntansha) 大崎 能伸  旭川医科大学, 大学病院, 客員教授 (30191935)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords多量体阻害 / 肺がん / 分子標的薬 / ペプチド療法 / 多量体形成 / EML4-ALK / EML4 / ALK / 肺腺癌 / 単量体化 / ペプチド創薬 / 融合遺伝子 / coilel-coil / 肺癌
Outline of Final Research Achievements

In this study, we investigated the molecular mechanism of EML4-ALK, one of the gene translocations responsible for lung cancer, which contributes to cancer cell growth through autophosphorylation. In our study, we focused on the EML4 protein, which is fused to ALK, and analyzed its function.
Since the multimeric EML4 molecule can be isolated and monomerized to suppress the growth of cancer cells, we prepared an analogous protein of the coiled-coil region of EML4 (CC peptide) and administered it to the cells. The cells in the CC peptide group showed 70-80% inhibition of cell proliferation compared to the non-treated group.

Academic Significance and Societal Importance of the Research Achievements

現在の肺癌ドライバー遺伝子陽性に対する治療は、低分子化合物による治療あるいは、高分子である抗体薬の治療が主体である。本研究では、ペプチド化合物(中分子)を用いることで従来の薬剤と異なる医薬品分類で安価に合成できるものである。
がん細胞内へのペプチドの取り込みなど課題はあるが、新しい視点でのがん治療の基礎となる研究である。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (2 results)

All 2020 2019

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

  • [Journal Article] Monomerization of ALK Fusion Proteins as a Therapeutic Strategy in ALK-Rearranged Non-small Cell Lung Cancers2020

    • Author(s)
      Hirai Noriko、Sasaki Takaaki、Okumura Shunsuke、Minami Yoshinori、Chiba Shinichi、Ohsaki Yoshinobu
    • Journal Title

      Frontiers in Oncology

      Volume: 10 Pages: 419-428

    • DOI

      10.3389/fonc.2020.00419

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Monomerization of ALK fusion proteins as a therapeutic strategy in ALK rearranged cancers2019

    • Author(s)
      Noriko Hirai, Takaaki Sasaki, Yoshinobu Ohsaki
    • Organizer
      American Association of Cancer Research
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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