Development of a New Lung Cancer Therapy Using Inhibition of DNA Damage Repair by BET Inhibition

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17173
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Hokkaido University
• Principal Investigator: Takashima Yuta 北海道大学, 大学病院, 助教 (90848764)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 肺がん / パクリタキセル / DNA修復 / 非相同末端結合 / 細胞周期

Outline of Final Research Achievements

H1299 cells were paclitaxel (PTX) resistance and exhibited an increased frequency of mitotic slippage upon PTX treatment. The newly generated PTX-resistant cells (A549-PR) were even more prone to mitotic slippage following PTX treatment. NHEJ inhibitors significantly augmented the PTX-induced DNA double-strand breaks and cytotoxicity in H1299 cells and A549-PR cells. NHEJ inhibition may overcome intrinsic or acquired PTX resistance resulting from mitotic slippage by synergistically increasing the cytotoxic effects of antimitotic drugs in NSCLC.

Free Research Field

肺がん

Academic Significance and Societal Importance of the Research Achievements

非小細胞肺がんに対して使用されているPTXの耐性機序であるmitotic slippageによる細胞死の回避に対してDNA修復機構であるNHEJ機構の抑制が有効であることを示した初めての研究である。さらなる検討が必要だが、今後の肺癌治療の発展の一助となる可能性があると考える。