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Review
. 2021 Nov 10;22(22):12179.
doi: 10.3390/ijms222212179.

Molecular Mechanisms and Cellular Contribution from Lung Fibrosis to Lung Cancer Development

Anna Valeria Samarelli  1   2 , Valentina Masciale  1   3 , Beatrice Aramini  1   4 , Georgina Pamela Coló  5 , Roberto Tonelli  1   2   6 , Alessandro Marchioni  1   2 , Giulia Bruzzi  1   2 , Filippo Gozzi  1   2   6 , Dario Andrisani  1   2   6 , Ivana Castaniere  1   2   6 , Linda Manicardi  1   2 , Antonio Moretti  1   2 , Luca Tabbì  2 , Giorgia Guaitoli  3   6 , Stefania Cerri  1   2 , Massimo Dominici  1   3 , Enrico Clini  1   2
Affiliations
Review

Molecular Mechanisms and Cellular Contribution from Lung Fibrosis to Lung Cancer Development

Anna Valeria Samarelli et al. Int J Mol Sci. .

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease (ILD) of unknown aetiology, with a median survival of 2-4 years from the time of diagnosis. Although IPF has unknown aetiology by definition, there have been identified several risks factors increasing the probability of the onset and progression of the disease in IPF patients such as cigarette smoking and environmental risk factors associated with domestic and occupational exposure. Among them, cigarette smoking together with concomitant emphysema might predispose IPF patients to lung cancer (LC), mostly to non-small cell lung cancer (NSCLC), increasing the risk of lung cancer development. To this purpose, IPF and LC share several cellular and molecular processes driving the progression of both pathologies such as fibroblast transition proliferation and activation, endoplasmic reticulum stress, oxidative stress, and many genetic and epigenetic markers that predispose IPF patients to LC development. Nintedanib, a tyrosine-kinase inhibitor, was firstly developed as an anticancer drug and then recognized as an anti-fibrotic agent based on the common target molecular pathway. In this review our aim is to describe the updated studies on common cellular and molecular mechanisms between IPF and lung cancer, knowledge of which might help to find novel therapeutic targets for this disease combination.

Keywords: cancer associated fibroblasts (CAFs); idiopathic pulmonary fibrosis; lung cancer; mechanotrasduction; myofibroblast.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Common pathogenic mechanisms between lung cancer and IPF.
Figure 2
Figure 2
Origin and signalling pathway leading to the activation of myofibroblasts in IPF and CAFs in LC.
See this image and copyright information in PMC

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