Management and future directions in non-small cell lung cancer with known activating mutations.

摘要: Lung cancer accounts for a quarter of all deaths. Non-small cell lung (NSCLC) is currently segregated by the presence actionable driver oncogenes. This review will provide an overview molecular subsets cancer, including descriptions defining oncogenes (EGFR, ALK, KRAS, ROS1, RET, BRAF, ERBB2, NTRK1, FGFR, among others) and how these predict response to small molecule tyrosine kinase inhibitors (TKIs) that are either clinically available or in clinical trial development advanced NSCLC. Particular focus be placed on with EGFR mutated ALK rearranged Somatic TKI-sensitizing mutations (such as exon 19 deletions L858R substitutions) most robust predictive biomarker symptom improvement, radiographic response, increment progression-free survival (PFS) when TKIs (gefitinib, erlotinib, afatinib) used patients However, palliative benefits afford limited multiple biologic mechanisms tumor adaptation/resistance EGFR-T790M mutation oncogene bypass tracks), future efforts toward delaying, preventing, treating resistance underway. Similar mutations, rearrangements exemplify oncogene-driven NSCLC can effectively palliated precision TKI therapy (the multitargeted ALK/MET/ROS1 crizotinib). When first-line crizotinib occurs, second generation have demonstrated impressive rates disease control trials, may modify long-term outcomes ALK-positive The other NSCLCs expand portfolio therapies this recalcitrant cancer.