Background/Objectives:Pulmonary fibrosis (PF) and lung cancer (LC) are major global health challenges that share several pathogenic mechanisms despite their distinct clinical features. PF leads to progressive fibrotic remodeling and respiratory decline, while LC is characterized by uncontrolled proliferation, invasion, and metastasis. Growing evidence shows that PF markedly increases the risk of LC development. This review aims to clarify the convergent molecular and cellular mechanisms that link fibrogenesis to tumorigenesis.Methods:Published studies exploring shared pathogenic pathways, molecular signaling networks, immune microenvironment alterations, and mitochondrial and genomic disturbances in PF and LC were systematically examined and integrated to identify common mechanisms contributing to fibrosis-associated carcinogenesis.Results:Findings highlight several overlapping processes between PF and LC, including oxidative stress, genomic instability, dysregulated DNA damage repair, immune microenvironment remodeling, mitochondrial dysfunction, and alterations in the ubiquitin–proteasome system. These aberrations drive chronic inflammation, epithelial–mesenchymal transition (EMT), extracellular matrix (ECM) remodeling, and other hallmarks shared by both diseases. Key signaling pathways—such as transforming growth factor-β (TGF-β), programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1), and tumor microenvironment–mediated immune evasion—further contribute to disease progression and increased LC risk in PF patients.Conclusions:Integrating molecular and pathological insights reveals a strong biological continuum between PF and LC. Understanding these convergent mechanisms may facilitate the identification of diagnostic biomarkers and therapeutic targets, ultimately helping to mitigate PF-associated lung carcinogenesis.
背景/目的：肺纤维化与肺癌是全球性的重大健康挑战，尽管两者临床表现各异，却共享多种致病机制。肺纤维化导致进行性纤维化重塑和呼吸功能衰退，而肺癌则以不受控制的增殖、侵袭和转移为特征。越来越多的证据表明，肺纤维化显著增加肺癌发生风险。本综述旨在阐明连接纤维化发生与肿瘤发生的共同分子和细胞机制。 方法：系统梳理并整合已发表的关于肺纤维化与肺癌共同致病通路、分子信号网络、免疫微环境改变以及线粒体和基因组紊乱的研究，以识别导致纤维化相关癌变的共同机制。 结果：研究结果凸显了肺纤维化与肺癌之间多个重叠的病理过程，包括氧化应激、基因组不稳定性、DNA损伤修复失调、免疫微环境重塑、线粒体功能障碍以及泛素-蛋白酶体系统改变。这些异常驱动了慢性炎症、上皮-间质转化、细胞外基质重塑等两病共有的特征性改变。关键信号通路——如转化生长因子-β、程序性死亡蛋白-1/程序性死亡配体-1以及肿瘤微环境介导的免疫逃逸——进一步促进了疾病进展，并增加了肺纤维化患者的肺癌风险。 结论：整合分子与病理学视角揭示了肺纤维化与肺癌之间存在紧密的生物学连续性。理解这些趋同机制有助于发现诊断生物标志物和治疗靶点，最终为减轻肺纤维化相关的肺癌发生提供新策略。
From Fibrosis to Malignancy: Mechanistic Intersections Driving Lung Cancer Progression
肿瘤(癌症)患者之家