title: Beyond histology: translating tumor genotypes into clinically effective targeted therapies.
abstract: Increased understanding of intertumoral heterogeneity at the genomic level has led to significant advancements in the treatment of solid tumors. Functional genomic alterations conferring sensitivity to targeted therapies can take many forms, and appropriate methods and tools are needed to detect these alterations. This review provides an update on genetic variability among solid tumors of similar histologic classification, using non-small cell lung cancer and melanoma as examples. We also discuss relevant technological platforms for discovery and diagnosis of clinically actionable variants and highlight the implications of specific genomic alterations for response to targeted therapy.
authors.affiliation: Authors' Affiliations: Departments of Cancer Biology, Medicine, Biomedical Informatics, and Pathology, Microbiology, and Immunology; Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Meador
authors.forename: Christine M
authors.initials: CM
authors.lastname: Micheel
authors.forename: Mia A
authors.initials: MA
authors.lastname: Levy
authors.forename: Christine M
authors.initials: CM
authors.lastname: Lovly
authors.forename: Leora
authors.initials: L
authors.lastname: Horn
authors.forename: Jeremy L
authors.initials: JL
authors.lastname: Warner
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Johnson
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Zhao
authors.forename: Ingrid A
authors.initials: IA
authors.lastname: Anderson
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Sosman
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Vnencak-Jones
authors.forename: Kimberly B
authors.initials: KB
authors.lastname: Dahlman
authors.forename: William
authors.initials: W
authors.lastname: Pao
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005820:Genetic Testing / Q000379:methods; D014644:Genetic Variation; D023281:Genomics / Q000379:methods; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D008545:Melanoma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D058990:Molecular Targeted Therapy; D009154:Mutation; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; D048493:Proto-Oncogene Proteins B-raf