Non-small cell lung cancer molecular characterization of advanced disease with focus on sex differences: a narrative review

Abstract

Molecular characterization is the basis of precision medicine in advanced non-small cell lung cancer (NSCLC), especially in the adenocarcinoma subtype. Determination of the molecular status of several predictive biomarkers (EGFR, ALK, ROS1, BRAF, RET, NTRK and PD-L1) is mandatory to tailor the therapy. Nowadays it is extremely clear that the definition of oncogene addiction and the evaluation of single biomarkers are insufficient to fully understand tumor biology and behaviour. In this context, peculiar molecular features with an impact on prognosis and a response to therapy can be related to sex differences. Lung cancer in non-smokers has been reported to be more frequent in women than in men, with a higher rate of driver and targetable alterations. A different molecular picture between men and women can depend on a sex-biased susceptibility to the carcinogenic effects of tobacco exposure and hormonal status. Although lung cancer in women has peculiar biological and clinical features, further studies are needed to better define sex-related molecular aspects and to evaluate to what extent they can improve personalized treatments.