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

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08132
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Asahikawa 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
• Keywords: 多量体阻害 / 肺がん / 分子標的薬 / ペプチド療法

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.

Free Research Field

癌の分子標的治療

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。