A novel postoperative therapeutic strategy for resected non-small cell lung cancer patients with idiopathic pulmonary fibrosis

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K08804
• 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: University of Miyazaki
• Principal Investigator: MAEDA RYO 宮崎大学, 医学部, 准教授 (00648769)
• Co-Investigator(Kenkyū-buntansha): 薄田 勝男 金沢医科大学, 医学部, 非常勤講師 (00324046) ; 浦本 秀隆 金沢医科大学, 医学部, 教授 (90389445)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 間質性肺炎 / 肺癌 / 術後補助化学療法

Outline of Final Research Achievements

The 5-year recurrence-free proportion for patients with idiopathic pulmonary fibrosis (IPF) was significantly lower than that for patients without IPF (48.5% and 87.1%, respectively; p < 0.001). The presence of IPF was a statistically significant independent risk factors for recurrence in a multivariate analyses (p = 0.019). Compared with patients without IPF, postoperative lung metastasis was more frequently found in patients with IPF (p = 0.003). From these results, we hypothesized that the lung microenvironment of IPF was associated with postoperative recurrence to the lungs. In vivo murine model of bleomycin (BLM)-induced IPF, the lung microenvironment of IPF promoted the lung metastases of cancer cells. In addition, the pharmacological treatment of the IPF by Pirfenidone inhibited lung metastasis of lung cancer cells promoted by BLM-induced IPF lung microenvironment in our in vivo model.

Free Research Field

呼吸器外科学

Academic Significance and Societal Importance of the Research Achievements

病理病期I期の間質性肺炎合併肺癌の切除症例を検討したところ、非合併肺癌と比較して、肺転移による再発が有意に多いことを見出した。この臨床研究より得られた結果から、「間質性肺炎における肺の環境が、肺癌の肺転移巣の形成を促進させる」という新規の仮説を立て、この独自の作業仮説をマウスモデルで検証した。同時に、間質性肺炎を合併した肺癌の術後に、抗線維化薬を投与し間質性肺炎を制御することで、肺転移による再発を抑制することができることを示した。本研究から、間質性肺炎合併肺癌に対する新たな術後の治療戦略を提唱できたと考えている。