Why many lung cancer patients who have never smoked have worse outcomes

Lung cancer is the most common 2.5 million new cases worldwide. We usually associate this disease with smokers because they are more likely to suffer from it. However, controversially, there is a small proportion of those who have never tried tobacco and who, unfortunately, respond worse to treatment. And now a group of scientists has found the reason. We tell you.

Research published in Natural communicationsshows that lung cancer cells with two specific genetic mutations

They duplicate their genome more often, that is, they are more resistant to treatment. Non-small cell lung cancer (NSCLC) is the most common cancer in non-smokers.

In the UK, where this study was conducted, 15% of NSCLC cases carry a specific mutation in epidermal growth factor receptor gene (EFFR). Most of them are non-smokers.

Lung cancer with this mutation is treated with a class of drugs called EGFR inhibitors. They have been in use for 15 years and usually give very good results for smokers and former smokers. However, they do not work in patients with additional p53 gene mutation, which is responsible for suppressing tumors. In these cases, the tumors do not shrink, and in other cases they even grow. Both mutations are more common in non-smokers.

Therefore, there are two mutations: in EGFR and p53. Is this the reason why non-smokers have worse outcomes? The researchers saw that all patients who only had the EGFR mutation experienced a significant reduction in tumor size. However, those who also had a p53 mutationmost of whom are non-smokers, are less fortunate.

“We showed why the presence of a p53 mutation is associated with worse survival in patients with lung cancer not associated with smoking, which is combination of EGFR and p53 mutationsallowing genome duplication to increase risk develop drug-resistant cells due to chromosomal instability,” said Professor Charles Swanton, PhD, from the UCL Cancer Institute and the Francis Crick Institute.

With these results, once patients with EGFR and p53 mutations and complete genome duplications are identified, they can be treated. be more selective.