Molecular characterization into clinical practice: current status and future perspectives in metastatic non-small-cell lung cancer

Non-small-cell lung cancer (NSCLC) is a common malignant disease, characterized by extremely poor prognosis. Until recently, treatment of advanced disease was based on platinum based chemotherapy, leading to great heterogeneity in terms of effectiveness, with median overall survival in the unselected population of less than one year. However, recent knowledge about genetic alterations in subsets of NSCLC has changed the clinical approach to metastatic disease. The primary efforts focus on targeted treatments that specifically inhibit vital signaling pathways. Successful examples of this new approach are the inhibition, by treating with erlotinib and gefitinib, of the epidermal growth factor receptor (EGFR) pathway in patients with EGFR mutations and the clinical development of crizotinib, effective in lung cancer harboring ALK rearrangements. Similarly, biological study concerning other molecular alterations characterizing specific subgroups of lung adenocarcinomas is likely to find clinical application soon. Genetic alterations in squamous cell carcinomas are less studied, but recent data suggest that their study could help in improving treatment also in this context. Molecular characterization can also be useful in improving chemotherapy efficacy and reducing toxicity by addressing the selection of chemoregemines.