2023 Fiscal Year Final Research Report

Development of novel treatments for lung cancer based on genetic heterogeneity

Research Project

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Project/Area Number	20K09168
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	Sugio Kenji 大分大学, 医学部, 教授 (70235927)
Co-Investigator(Kenkyū-buntansha)	宮脇美千代大分大学, 医学部, 講師 (30404388) 阿南健太郎大分大学, 医学部, 助教 (60468006) 橋本崇史大分大学, 医学部, 助教 (40738126) 小副川敦大分大学, 医学部, 准教授 (90432939)
Project Period (FY)	2020-04-01 – 2024-03-31
Keywords	遺伝子多様性 / 非小細胞肺癌 / 肺腺癌 / 進化系統樹 / EGFR / 分子モニタリング / バイオマーカー
Outline of Final Research Achievements	The 5-year survival rate of primary lung cancer is not satisfactory, and multidisciplinary treatment is essential. Intratumor genetic heterogeneity is an important factor that determines the sensitivity and resistance of treatment. First, EGFR mutations were detected in 81 cases, ALK in 4 cases, KRAS in 4 cases, RET in 1 case, and ERBB-2 in 1 case, in 194 surgical cases of lung adenocarcinoma. The genetic mutations in the plasma were investigated by NGS analysis at the time of postoperative recurrence in 4 patients with locally advanced non-small cell lung cancer, and molecular monitoring was presented. Furthermore, plasma cfDNA was analyzed from 26 cases of non-small cell lung cancer patients who underwent surgery, and in cases of recurrence, cfDNA was elevated before tumor markers increased, suggesting the possibility of early prediction of recurrence.
Free Research Field	呼吸器外科、腫瘍外科
Academic Significance and Societal Importance of the Research Achievements	ドライバー遺伝子変異陽性非小細胞肺癌の治療成績の向上のためには、分子標的治療の感受性をあげ、かつ耐性を克服することが重要である。本研究により、個々の症例の腫瘍内遺伝子多様性（不均一性）を正確に解析・理解することが腫瘍の進展の予測に有用で、経時的な分子モニタリングの手法を確立する一助となる。さらなるモニタリングの手法の確立が患者の予後向上に寄与することとなる。肺癌は全癌の中で最も死亡数の多い悪性腫瘍であり、その予後向上は社会的に極めて重要である。