Abstract
BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF), a chronic progressive interstitial lung disease of unknown etiology, is characterized by alveolar architecture destruction and progressive pulmonary parenchymal scarring, with an extremely poor prognosis. While antifibrotic therapies have been shown to slow disease progression in clinical practice, IPF patients continue to experience irreversible declines in pulmonary function. Notably, lung cancer (LC) represents a severe complication of IPF. IPF patients exhibit a 2.7-48% lifetime risk of LC development, with patients diagnosed with IPF with LC (IPF-LC) exhibiting significantly poorer prognoses than those with IPF alone. Furthermore, the rising prevalence of IPF-LC has rendered it a critical challenge in clinical management. The objective of this review is to provide a comprehensive analysis of the epidemiological characteristics, early diagnostic approaches, and therapeutic innovations in IPF-LC, with particular emphasis on emerging biomarkers and their clinical applications. METHODS: A literature search was conducted using PubMed, focusing on articles published in English from 2006 to August 2025. Studies focusing on IPF-LC diagnostic and therapeutic advancements were selected for in-depth analysis and incorporated into this review. KEY CONTENT AND FINDINGS: This review highlights the high incidence and poor prognosis of IPF progressing to IPF-LC, driven by common risk factors and molecular pathways. Early diagnosis relies on multidisciplinary evaluation, annual high-resolution computed tomography (HRCT), and biomarkers. Antifibrotic agents delay fibrosis, reduce cancer risk and may act synergistically with immuno- and chemotherapies, whereas surgery/radiotherapy needs to be chosen carefully due to the risk of acute exacerbation. CONCLUSIONS: Combining imaging with biomarkers will effectively increase the probability and reliability of early diagnosis of IPF-LC. Antifibrotic drugs not only slow IPF progression, but may also reduce LC risk by inhibiting the pro-fibrotic-cancerous common pathway and enhance the efficacy of chemotherapy and immunotherapy. Future studies could focus on validating biomarkers, optimizing combinations of antifibrotic and immunotherapies, and integrating artificial intelligence-driven diagnostics to improve outcomes.