Molecular basis for the cross-sectional vulnerability of various cancers elicited by atypical nucleic acid configuration and its therapeutic application

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19487
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: Seimiya Hiroyuki 公益財団法人がん研究会, がん化学療法センター 分子生物治療研究部, 部長 (50280623)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: グアニン4重鎖 / がん細胞 / 薬剤感受性 / 核酸

Outline of Final Research Achievements

Some types of cancer cells exhibit significant vulnerability to stabilization of G-quadruplex (G4), an atypical higher-order structure of nucleic acids. However, the molecular mechanism for such selective anti-proliferative effect remains elusive. In this study, we performed comparative analyses on G4-stabilizing chemical (G4 ligand)-sensitive and resistant cancer cells and identified ABCG2, a member of the ABC transporter family, as a resistant factor to a synthetic G4 ligand. Furthermore, we identified a candidate gene X, which knockdown by siRNAs alleviates resistance of cancer cells to G4 ligands.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

がん薬物療法を発達させるうえで、革新的新薬の創製と精度の高い効果予測法の確立が求められている。神経膠芽腫および膵がんはいずれも難治がんの代表格であり、これらの新薬開発は喫緊の課題である。本研究は、G4リガンドが神経膠芽腫に加えてある種の膵がんにも有効な創薬シーズである可能性を示した。さらに、本研究で同定されたG4リガンド感受性規定候補因子が同剤の治療効果を予測するバイオマーカーとなる可能性が示唆された。