Chest
Volume 156, Issue 2, August 2019, Pages 383-391
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Translating Basic Research Into Clinical Practice
Common Pathogenic Mechanisms Between Idiopathic Pulmonary Fibrosis and Lung Cancer

https://doi.org/10.1016/j.chest.2019.04.114Get rights and content

Abundant epidemiologic evidence supports an association between idiopathic pulmonary fibrosis (IPF) and lung cancer. Lung tumors in patients with IPF develop preferentially in the periphery immediately adjacent to fibrotic areas, with different histologic distribution and immunohistochemical features compared with non-IPF-associated lung tumors. In this context, evidence indicates that IPF and lung cancer share many pathogenic similarities including genetic and epigenetic markers. It has been suggested that specific germline mutations predispose toward both IPF and lung cancer, leading to imbalance between oncogenes and tumor suppressor genes and ultimately carcinogenesis within fibrotic lungs. Aberrant epigenetic regulation due to methylation, histone modifications, and mainly deregulation of common noncoding RNAs represents a possible pathogenic link between the two disease paradigms. Genetic and epigenetic alterations lead to abnormal activation of common transduction pathways, including Wnt/β-catenin and phosphoinositide 3-kinase/protein kinase B, mediating metaplasia and hyperproliferation in alveolar type II epithelial cells. Cellular transformations in the mesenchymal phenotype represent a common link between lung fibrosis and carcinogenesis. In this review we summarize current data on common cellular and molecular pathogenic mechanisms between IPF and lung cancer and highlight promising therapeutic targets for this disease combination.

Section snippets

Genetics

Although the pathogenesis of IPF is not well understood there is a growing body of evidence that genetic variants may explain the risk of disease development and progression, as well as treatment response.10 Large genome wide-association studies have indicated that almost one-third of the risk of developing a fibrotic idiopathic interstitial pneumonia can be explained by genetic variants including MUC5B, telomerase, and surfactant-associated genes (Table 1).10 On the other hand, lung cancer

Conclusion

Current data support the idea that the coexistence of IPF and lung cancer cannot be coincidental. IPF and lung cancer may represent the complex result of immune privilege, that is, a metaplastic respiratory epithelium that evades immune surveillance due to interaction with a fibrotic stroma, which provides all necessary epigenetic signals that mediate neoplasia in genetically predisposed individuals. However, how diffuse interstitial lung abnormalities produce focal cancerous lesions is still

Acknowledgments

Financial/nonfinancial disclosures: The authors have reported to CHEST the following: D. B. has received travel grants, consultancy fees, and money for patient enrollment/research completion and speaking activities from Hoffmann-La Roche and Boehringer Ingelheim. A. T. has received travel, honorary, and consultancy fees from Boehringer Ingelheim, Hoffmann-La Roche, Elpen, Chiesi, and AstraZeneca. V. T. has received travel fees from Boehringer Ingelheim and Hoffmann-La Roche. None declared (G.

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    Drs Tzouvelekis and Gomatou contributed equally to this manuscript.

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