title: The evolving genomic classification of lung cancer.
abstract: EGFR gene mutations and ALK gene fusions are well-characterized molecular targets in NSCLC. Activating alterations in a variety of potential oncogenic driver genes have also been identified in NSCLC, including ROS1, RET, MET, HER2, and BRAF. Together with EGFR and ALK, these mutations account for ∼20% of NSCLCs. The identification of these oncogenic drivers has led to the design of rationally targeted therapies that have produced superior clinical outcomes in tumours harbouring these mutations. Many patients, however, have de novo or acquired resistance to these therapies. In addition, most NSCLCs are genetically complex tumours harbouring multiple potential activating events. For these patients, disease subsets are likely to be defined by combination strategies involving a number of targeted agents. These targets include FGFR1, PTEN, MET, MEK, PD-1/PD-L1, and NaPi2b. In light of the myriad new biomarkers and targeted agents, multiplex testing strategies will be invaluable in identifying the appropriate patients for each therapy and enabling targeted agents to be channelled to the patients most likely to gain benefit. The challenge now is how best to interpret the results of these genomic tests, in the context of other clinical data, to optimize treatment choices in NSCLC.
authors.affiliation: Genentech Inc, South San Francisco, California, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Shames
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D023281:Genomics / Q000379:methods; D006801:Humans; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D058990:Molecular Targeted Therapy; D018579:Patient Selection; D010641:Phenotype
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
keywords: ALK; EGFR; NSCLC; biomarkers; genomic classification; lung cancer; molecular targets; monoclonal antibodies; multiplex testing; tyrosine-kinase inhibitors