Analysis of the drug persistent cells to understand the acquired resistance mechanisms in lung cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03524
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: KATAYAMA Ryohei 公益財団法人がん研究会, がん化学療法センター 基礎研究部, 部長 (60435542)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 薬剤耐性 / 分子標的薬 / 治療残存細胞

Outline of Final Research Achievements

Recently, development of molecular-targeted drugs and cancer immunotherapy remarkably improved the prognosis of advanced lung cancer, but the emergence of acquired resistance and primary resistance in a certain fraction of patients are major obstacles to further improve cancer therapy. In this study, we investigated when and how drug resistant cancer emerges, by focusing on the drug tolerant persister cells that could be a seed of drug-resistance, and explored therapeutic target molecules, pathways, and therapeutic strategies. We discovered that GSK3 could be a potential target in drug tolerant persister cells in ALK-rearranged lung cancer. In addition, we successfully found and published a new effective drug candidate for multidrug-resistant ALK-TKI resistant compound mutations.

Free Research Field

腫瘍学

Academic Significance and Societal Importance of the Research Achievements

進行がんの治療は目覚ましく進歩しているが、耐性出現が免れられないため、治療時にもわずかに残る細胞の性状解析から耐性細胞出現を抑制したり遅くしたりすることが期待できる。本研究で見出した治療残存細胞の新たな治療標的候補発見はこれまでに報告の無い新たな因子の関与を見出したものであり学術的意義は高い。なお、本研究で見出した多剤耐性変異型ALKにも有効な治療法候補の発見は、他のがんを対象とした既存薬による治療応用の可能性についての研究であり、臨床応用へとつなげることができると学術的および社会的意義の高い研究となることが期待できる。