New anti-cancer therapy targeting therapy-induced senescent cancer cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07177
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Shimane University
• Principal Investigator: Harada Mamoru 島根大学, 学術研究院医学・看護学系, 教授 (50260716)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: がん免疫療法 / 腫瘍生物学 / 複合的がん治療法

Outline of Final Research Achievements

Anti-cancer drugs have been used to induce cancer cell death, whereas some cancer cells survive via slowing cell cycle, called senescence, as a result of DNA damage responses. These therapy-induced senescent cancer cells have been considered as responsible cells for recurrence. Alternatively, several drugs that selectively kill senescent cells have been reported recently. ABT-263 (navitoclax), a Bcl-2/xL inhibitor, is a representative of them. In this research project, we revealed that senescence was induced in human breast, lung and pancreatic cancer cell lines when treated with abemaciclib, pemetrexed or gemcitabine, respectively. In addition, such senescent cancer cells were effectively killed by ABT-263. These results indicate a possibility of effective combined anti-cancer therapy having the potential to induce complete cure of cancer.

Free Research Field

がん免疫治療学

Academic Significance and Societal Importance of the Research Achievements

抗がん化学療法剤や分子標的薬などの抗がん剤は、本邦でのがん治療の中心となっている。しかし、これらの抗がん剤で一時的にはがんの退縮を認めても、多くの場合、再発してしまう。その機序として、がん治療後に残存した老化がん細胞が再発にかかわっている可能性が示唆されている。申請者は、抗がん剤治療後に残存した老化がん細胞を選択的に破壊する薬剤を用いてがんの根治を目指した複合的がん治療モデルの検証を多種類のヒトがん細胞を用いて実施し、この治療プロトコールが有効であることを示した。これらの成果は、がんの根治を期待できる複合的がん治療の可能性を示しており、がん治療効果を高めるために貴重な情報となると考えられる。