• Bo Mi Ku, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, and Myung-Ju Ahn.
• a Samsung Biomedical Research Institute, Samsung Medical Center , Sungkyunkwan University School of Medicine , Seoul , Korea.
• Expert Rev. Mol. Diagn. 2017 Oct 1; 17 (10): 933-942.

IntroductionThe discovery of activating genetic and their use as predictive biomarkers for targeted therapy, such as tyrosine kinase inhibitors (TKIs), has changed the treatment paradigm of non-small cell lung cancer (NSCLC). As a result, epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) TKIs have become the standard first-line treatment. Since then, other kinds of targetable oncogenic alterations have been identified in NSCLC. Several novel, molecularly-targeted TKIs have now achieved regulatory approval, while many others are currently in early- or late-phase clinical trial testing. These TKIs have significantly impacted and changed clinical outcomes for advanced NSCLC. Areas covered: In this review, the authors discuss recent evidence and progress in targeted therapies, especially small molecular tyrosine kinase inhibitors, matched with their biomarkers for the treatment of advanced NSCLC. Expert commentary: Although targeted therapies dramatically improve the outcome of patients with NSCLC harboring specific oncogenic alterations, molecular and clinical resistance almost invariably develops. New TKIs specifically active in molecular subgroups of NSCLC or the resistance setting have now been developed. The development of additional TKIs and rational combinations may further improve outcomes of NSCLC.

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