05 October 2021

Lung cancer in non-smokers

Despite the proven role of smoking in the occurrence of lung cancer, a significant number of patients who develop such tumors have never smoked and have not been exposed to strong tobacco smoke. In the US, up to 15% of lung cancer cases are diagnosed in people who have never smoked, in some parts of Asia, this proportion can reach 40%.

A study conducted by scientists at Washington University Medical School in St. Louis and Barnes-Jewish Hospital demonstrates new possibilities for the treatment of these patients.

Researchers have found that the vast majority of non-smoking patients with lung tumors have genetic changes that doctors can affect with already approved drugs.

The researchers analyzed the material obtained from 160 patients with lung adenocarcinoma without a history of tobacco smoking. They showed that from 78% to 92% of cases can be treated with already approved drugs targeting specific mutations in the tumor. In most cases, non–smokers in lung tumors had so-called driver mutations - specific errors in DNA that contribute to tumor growth and that can be blocked with drugs. Smokers had such mutations only in half of the cases.

To characterize different types of cancer, scientists compared the data of study participants with data from smokers and those who have never smoked from The Cancer Genome Atlas and the Clinical Proteomic Tumor Analysis Consortium, projects led by the National Institutes of Health (NIH). Scientists verified the status of a non-smoker by studying mutational patterns in these patients and comparing them with mutational patterns of lung cancer in patients who smoked.

Past work carried out by the group has shown that lung tumors in smokers have 10 times more mutations than in non-smokers, but such mutations are rarely found in smokers' tumors. In other words, lung tumors of people who have never smoked have unique features that are not characteristic of smokers.

Only 7% of non-smoking patients already had mutations at birth that increased the risk of developing cancer. About 60% of these tumors are found in women and 40% in men. Lung cancer in general affects men more often, but cancer in non-smokers for unknown reasons is more common in women. It is possible that non-smoking patients have a hereditary predisposition, which has not yet been determined.

The study also shed light on the immune profiles of tumors in non-smokers, which may explain why most of them do not respond well to immunotherapy with checkpoint inhibitors. Unlike the studied lung tumors of smokers, a small proportion of the tumors of non-smokers contained immune cells or immune response-regulating molecules that checkpoint inhibitors trigger to fight cancer.

The results obtained in this study emphasize the need for high-quality biopsy to obtain tumor samples and their clinical genomic testing in non-smoking patients, which will allow choosing the optimal treatment method.

Article by S.Devarakonda et al. Genomic Profiling of Lung Adenocarcinoma in Never-Smokers is published in the Journal of Clinical Oncology.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on Washington University School of Medicine: Most cases of never-smokers' lung cancer treatable with mutation-targeting drugs.

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