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[Genomics of lung adenocarcinoma: pathogenetic significance and clinical applications.]

Diagnostic and therapeutic approaches to non small cell lung cancer (NSCLC), especially adenocarcinoma, have recently undergone dramatic evolution according to the tremendous amount of molecular data collected on this cancer. In fact, the application of oncogenomics has identified novel molecular subtypes of NSCLC and led the way to diagnostic criteria based on the expression of specific genetic alterations that can provide prognostic and specific indications to the molecular targeted therapies. In NSCLC, several genes show "driver" molecular alterations that confer oncogenic potential to progenitor cells through the enrollment of metabolic pathways critical for cell proliferation and tumor development. On the other hand, clinical management of NSCLC with small molecules has undoubtedly provided optimistic results with both a significant increase in overall survival and reduction in therapy-related toxicity including relative complications. Thus, pharmacogenomics, as the newest tool for using the targeted therapy represents the most innovative approach for treatment of this cancer once the molecular aberrations are identified. In particular, the relative mutational status of several driver genes including EGFR, ALK, ROS1 and others, is directly correlated to a better response to thyrosin-kinase inhibitors. Furthermore, other therapeutic strategies with inhibitors of angiogenic receptors, PARP, histone-deacetylase, PI3K and HSP90, are intensively studied in pre-clinical models as well as in clinical trials for a potential adoption in clinical practice. The introduction of more advanced techniques for molecular profiling also allows to identify pathogenic variants of many other genes involved in the progression of lung adenocarcinoma with the aim to develop novel molecular targets for pharmacological research. In this review, we will revisit the current applications of oncogenomics in the diagnosis and treatment of this tumor.