title: Refining the treatment of NSCLC according to histological and molecular subtypes.
abstract: In the past decade, the characterization of non-small-cell lung cancer (NSCLC) into subtypes based on genotype and histology has resulted in dramatic improvements in disease outcome in select patient subgroups. In particular, molecularly targeted agents that inhibit EGFR or ALK are approved for the treatment of NSCLC harbouring genetic alterations in the genes encoding these proteins. Although acquired resistance usually limits the duration of response to these therapies, a number of new agents have proven effective at tackling specific resistance mechanisms to first-generation inhibitors. Large initiatives are starting to address the role of biomarker-driven targeted therapy in squamous lung cancers, and in the adjuvant setting. Immunotherapy undeniably holds great promise and our understanding of subsets of NSCLC based on patterns of immune response is continuing to evolve. In addition, efforts are underway to identify rare genomic subsets through genomic screening, functional studies, and molecular characterization of exceptional responders. This Review provides an overview of the key developments in the treatment of NSCLC, and discusses potential strategies to further optimize therapy by targeting disease subtypes.
authors.affiliation: Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, Building 10, 4-4553, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1201, USA.
authors.forename: Anish
authors.initials: A
authors.lastname: Thomas
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road North West, Washington, DC 20057, USA.
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Liu
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road North West, Washington, DC 20057, USA.
authors.forename: Deepa S
authors.initials: DS
authors.lastname: Subramaniam
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road North West, Washington, DC 20057, USA.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giaccone
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D018773:Genes, erbB-1 / Q000235:genetics; D006801:Humans; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D058990:Molecular Targeted Therapy; D057285:Precision Medicine; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases