Genetic and molecular mechanisms in lung cancer with interstitial pneumonia

Idiopathic pulmonary fibrosis (IPF) is associated with an increased risk of lung cancer, with cumulative incidence rates of 3.3% and 15.4% at 1 and 5 years of follow-up, respectively. The prognosis for patients with lung cancer and IPF is worse than that for patients with IPF alone, primarily due to the progression of lung cancer and complications arising after treatment. Epidemiological and molecular studies indicate that IPF and lung cancer share several pathogenic mechanisms, including genetic and epigenetic alterations. Germline mutations may contribute to both conditions by disrupting the balance between oncogenes and tumor suppressor genes, thereby driving carcinogenesis in fibrotic lungs. Epigenetic dysregulation, such as DNA methylation changes, histone modifications, and deregulation of noncoding RNAs, serves as a common link between these diseases by activating key signaling pathways, including Wnt/β-catenin and PI3K/Akt. These pathways promote alveolar type II cell hyperproliferation and metaplasia, both of which are critical processes in disease progression. In addition, mesenchymal transitions represent a shared pathological feature of lung fibrosis and tumorigenesis. In this review, we summarize the current molecular insights into lung carcinogenesis in lung cancer with IPF. Furthermore, we present findings from our recent comprehensive genetic analysis, which identifies distinct gene profiles indicative of unique carcinogenic mechanisms in lung cancer with IPF. These insights may contribute to improved risk assessment, early detection strategies, and the development of targeted therapies for lung cancer patients with IPF.