The Fibrotic-Cancer Continuum in IPF: Shared Mechanisms, Clinical Implications and Therapeutic Challenges

Idiopathic pulmonary fibrosis represents a chronic, progressive, lethal lung disease of various etiologies exerting a dramatic impact on patients' survival and quality of life. Its increasing prevalence and high mortality rates indicate the importance of early diagnosis and management involving the assessment of specific comorbidities, such as lung cancer. Emerging evidence suggests that in the context of IPF, lung scarring may be a potential risk factor for lung cancer development. Both disease entities present pathogenic commonalities including genetic and epigenetic markers, signaling pathways and cell transformation obtaining mesenchymal phenotypes. Beyond understanding disease pathogenesis, anti-cancer drugs such as nintedanib have been successfully used to treat patients with IPF. Additionally, a therapeutic approach that includes a mix of various pleiotropic anti-fibrotic agents is currently being developed for IPF treatment. Currently, there is no consensus on the application of therapeutic algorithms in concurrent pulmonary fibrosis and lung tumors. This review summarizes the current state of knowledge on common cellular and molecular pathogenetic mechanisms of IPF and lung cancer and highlights potential therapeutic targets with fruitful results.