The storm of NGS in NSCLC diagnostic-therapeutic pathway: How to sun the real clinical practice

[Display omitted] •Several guidelines suggest broad molecular profiling of NSCLC.•NGS represents a valid technologic option for multi-targeted assay.•The NSCLC sample triage is essential for NGS application in clinical practice.•NGS opportunities and challenges should be evaluated before clinical implementation.•A testing algorithm with indication for recent NSCLC targeted drug is herein proposed. The increasing number of approved drugs along with next generation sequencing (NGS) technologies look out as potential revolution of biomolecular characterization of non-small-cell lung cancer (NSCLC). Nevertheless, several aspects impact on success rate of NGS in clinical practice: a multidisciplinary approach and thorough knowledge of strengths and limits of each technologic diagnostic tool are required. Crucial preliminary step is the selection of the best available sample before testing, aware of clinical condition and setting of disease. Genomic data should be than integrated in the clinical context and matched with available therapeutic options; Molecular Tumor Boards (MTB) are worldwide emerging interdisciplinary groups implemented to transfer the impact of precision medicine in clinical practice. In order to guarantee equity in treatment, these considerations should find their application widely and rapidly. Aim of this review is offering an overview of emerging biomarkers, relative upcoming targeted drugs, and new diagnostic chances with an authors’ perspective about a real-life diagnostic-therapeutic algorithm useful for daily clinical practice.