The oncogenic landscape of the idiopathic pulmonary fibrosis: a narrative review

Abstract

Background and Objective: Translational research is a source of continuous innovation in medicine, more particularly for clinical research on new treatment modalities in idiopathic pulmonary fibrosis (IPF) patients.However, the heterogeneity of the disease is well recognized, and different pathological and molecular settings have been identified. The molecular mechanisms by which IPF proceeds in time and space remains poorly understood. Although some IPF features are reminiscent of cancer, the dynamics of malignant divergent clonal selective pressure and heterogeneity clearly differ from those occurring in IPF. This is reflected in the absence of patient proper selection and stratification to biological agents (pirfenidone, nintedanib) which limit therapeutic efficacy. Consequently, increased costs are related to the clinical management of advanced IPF patients. Steady collaboration and fluid communication between pneumo-oncologists, radiologists and molecular biologists is a clear priority for the correct interpretation of tests and the definition of effective personalized strategies against this orphan disease. The present work aims at providing the most relevant hints shared by cancer and IPF.Methods: A systematic literature review was performed to identify all relevant data. The examined databases were Scopus, Web of Science, Cochrane, Google Scholar, and PubMed. The last search was run on January 5, 2022. We have primarily conducted separated research for lung cancer, IPF, genetics, epigenetics, surgery in IPF and cancer.

Immunotherapy-related pneumonitis and the synergic impact of thoracic radiation and preexisting interstitial lung disease

“…In experimental studies with mice, PD-L1 expression was noted to be higher in injury-activated alveolar epithelial cells and in human donor samples with end-stage IPF [58 ▪ ], suggesting that disinhibition of immune cells might exacerbate this injured tissue. Though IPF and lung cancer are not often thought to share common genetic pathways, several genes that drive inflammation and fibrosis in IPF are also overexpressed in lung cancer, including TGF-β1, IL-1 receptor alpha, IL-4, IL-8, and others [59,60 ▪ ]. The shared genetic landscape of IPF and NSCLC has led to the use of antifibrotics to treat NSCLC, though evidence of efficacy is yet lacking [61,62 ▪ ].…”

The Genetic and Epigenetic Footprint in Idiopathic Pulmonary Fibrosis and Familial Pulmonary Fibrosis: A State-of-the-Art Review

“…The TP53 gene was found to be significantly mutated in cases of lung cancer associated with IPF. Mutations in the JAK-STAT signaling pathway were also significantly amplified in IPF-associated lung cancer [ 114 ].…”

Idiopathic pulmonary fibrosis and lung cancer: future directions and challenges

“…This interaction leads to the suppression of the immune response, which contributes to the pathogenesis of these diseases [ 24 ]. The MET signalling pathway (a receptor tyrosine kinase whose ligand is hepatocyte growth factor) is a major regulator of cell growth and proliferation and is activated in both IPF and lung cancer in response to hypoxia [ 2 , 26 ]. Its activation in different cancers leads to increased cell proliferation and tumour growth and increased expression of a number of genes involved in cell proliferation [ 27 ].…”

“…The association between pulmonary fibrosis and lung cancer is not a new topic. Papers have been written about this since the 1960s [ 2 , 39 , 40 ]. Hyperplasia and metaplasia seen in IPF may lead to additional transformation and cancer development [ 41 ].…”

“…It is occurring more frequently as the population is living longer [ 1 ]. Fibrosis is even more devastating because it is associated with an increased risk for lung cancer [ 2 ]. A large Korean population study reported that 1.2% of the overall population developed lung cancer; however, the percentage increased to 5% in patients with emphysema and to nearly 6% in those with fibrosis.…”