Targeting cell cycle-related genes in non-small cell lung cancer harboring driver mutations

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08889
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Oita University
• Principal Investigator: Osoegawa Atsushi 大分大学, 医学部, 准教授 (90432939)
• Co-Investigator(Kenkyū-buntansha): 宮脇 美千代 大分大学, 医学部, 講師 (30404388) ; 杉尾 賢二 大分大学, 医学部, 教授 (70235927)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 上皮成長因子受容体 / 細胞周期

Outline of Final Research Achievements

We conducted analyses using clinical specimens and cell lines to investigate the association between cyclin D1 expression and prognosis in cases of surgically resected EGFR-mutant positive lung cancer, and to examine the combined effects of EGFR-TKI and CDK4/6 inhibitors in EGFR-mutant positive lung cancer cell lines. In cell lines, a synergistic effect of the combination was observed, which could be explained by changes in signaling pathways and cell cycle. However, in clinical specimens, high expression of cyclin D1 was more commonly found in females and non-smokers, and the group with high cyclin D1 expression tended to have a better prognosis than the low expression group. It is considered that, in lung cancer, there are other therapeutic targets involved in malignancy besides cyclin D1, and ERβ may be involved.

Free Research Field

呼吸器外科学

Academic Significance and Societal Importance of the Research Achievements

上皮成長因子受容体(EGFR)変異陽性肺癌では、チロシンキナーゼ阻害剤（TKI）が奏効するが、進行再発症例においては約1.5年で耐性となるため、初期治療の強化が必要である。EGFR変異陽性肺癌では、細胞周期の異常を高頻度に認めるため、乳癌で広く用いられているCDK4/6阻害剤の併用効果を検討し、細胞株においてはEGFR-TKIとCDK4/6阻害剤の相乗効果と、その機序を明らかにした。一方、その標的であるcyclin D1は肺癌において予後良好な集団に発現しており、cyclin D1以外の標的を明らかにする必要がある。これらを明らかにしたことは学術的意義があると考えられる。