French Researchers Find 41 Mutations in Lung Cancers Associated with Pulmonary Fibrosis

French researchers have identified 41 gene mutations in lung cancers associated with pulmonary fibrosis, a discovery that could lead to new therapy targets for both diseases.

The findings applied to both non-idiopathic and idiopathic pulmonary fibrosis. Non-idiopathic cases are those that doctors have found a cause for, while Idiopathic cases have no known cause.

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

Idiopathic pulmonary fibrosis, or IPF, is a chronic disease with a median survival of only three years after diagnosis. IPF patients have a higher rate of lung cancer than the population at large, further worsening their prognosis.

Both IPF and lung cancer are associated with tobacco smoking, and studies suggest the conditions have common disease pathways.

IPF patients’ lung impairment makes it difficult for doctors to treat their lung cancer. But recent advances in treatment, such as therapies based on the disease’s molecular characteristics and biomarkers, have increased doctors’ success against it.

Two forms that doctors have achieved more success with are adenocarcinoma, the most common lung cancer, and squamous cell carcinoma, a large cell lung cancer.

Therapies against these forms target mutations of the EGFR, ALK and ROS1 genes associated with lung cancer. Another target is the PD-1/PD-L1 molecular pathway, which can bolster tumors’ ability to evade an immune response.

A French team hoped to find new therapy targets for lung cancer associated with both non-idiopathic and idiopathic pulmonary fibrosis. Dr. Aurelie Cazes of the Assistance Publique-Hôpitaux in Paris led the research.

The study involved 31 cancer samples collected from 2001 to 2016 at two French PF centers. Eighteen samples were from IPF patients, and 13 from non-IPF patients. The team did molecular analyses of 22 cancer-associated genes.

Squamous cell carcinoma was the most frequent cancer subtype in the IPF samples, occurring in 44 percent of the samples examined. Adenocarcinoma was the most prevalent cancer in the non-IPF cases, showing up in 62 percent of samples.

The analysis yielded 41 mutations of 13 genes, with the faulty genes showing up in 25 of the 31 samples. The mutations included the MET, FGFR3, SMAD4 and CTNNB1 genes, all of which “could potentially be involved in the lung fibrosis process,” the researchers wrote.

Another mutation was in the FBXW7 gene, which is involved in tumor suppression.

The team found no mutations of the EGFR, ALK and ROS1 genes. They also found low levels of PD-L1 in all but one tissue sample, suggesting that immunotherapy would not be the best treatment strategy in these patients.

A key takeaway from the study was that molecular alterations showed up in cancers associated with PF, a finding that could increase understanding of tumor biology.

“This extensive characterization of lung fibrosis-associated cancers evidenced molecular alterations which could represent either potential therapeutic targets or clues to the pathophysiology of these particular tumors,” the researchers wrote. “These findings support the relevance of large-scale molecular characterization of every lung fibrosis-associated cancer.”