Pulmonary Fibrosis Patients May Have Genetic Susceptibility to Lung Cancer, Study Shows

Pulmonary Fibrosis Patients May Have Genetic Susceptibility to Lung Cancer, Study Shows

Pulmonary fibrosis (PF) patients with lung cancer have alterations in 14 cancer-driver genes, a new French study analyzing cancer samples from PF patients reported.

The study is titled, “Morphologic and molecular study of lung cancers associated with idiopathic pulmonary fibrosis and other pulmonary fibroses,” and was published in the journal Respiratory Research.

The lungs of PF patients undergo chronic inflammatory and fibrotic processes, which may promote the development of lung cancer. Because of their lung dysfunction, PF patients are more susceptible to the negative effects of cancer treatments such as surgery, radiation, and chemotherapy.

To identify other therapeutic targets, researchers looked for tissue and gene alterations in PF patients. They identified 31 PF patients with lung cancer in French clinical and pathological databases. Of these, 18 patients were diagnosed with idiopathic pulmonary fibrosis (IPF), and 13 patients had other lung fibrotic diseases.

Based on tissue cancer analysis, the team found that IPF patients had mainly the squamous cell carcinoma cancer subtype (44%), while the majority of non-IPF patients had adenocarcinoma (62%).

Researchers extracted DNA from collected samples and sequenced a panel of 22 colon and lung cancer-associated genes.

In 25 samples, they found 41 mutations in 13 genes and amplification in the EGFR gene. The most-detected mutations (20) were in the TP53 gene and are likely associated with tobacco smoking. Other mutations were found in the genes MET, BRAF, FGFR3, PIK3CA, PTEN, STK11, SMAD4, CTNNB1, DDR2, ERBB4, FBXW7, and KRAS. Only two samples had no mutations in the selected panel of genes.

One of the therapies against lung cancer targets PD-L1, a protein that helps cancer cells to escape the antitumor immune response. However, in this group of patients, PD-L1 expression was low and therefore is not a strong candidate of immunotherapy in PF patients.

Researchers think that in PF patients, fibrosis-associated cancers may have specific molecular alterations. In the future, larger studies may further contribute to understanding how lung cancer evolves in the fibrotic lung to identify therapeutic targets.

An increase in extended survival in PF patients also increases the number of cancer cases, presenting a challenge for healthcare providers.

“Two recently approved drugs, pirfenidone [Esbriet] and nintedanib [Ofev], have been shown to slow IPF progression, and are expected to extend survival. If confirmed this may lead to an increase of challenging cancer cases and encourage to perform a large molecular characterization to every lung fibrosis-associated cancer,” the authors wrote.

More insights about gene mutations in lung fibrosis-associated cancers may reveal potential therapeutic targets for the disease, and offer a better understanding of the pathophysiology of these particular tumors.

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