title: From targets to targeted therapies and molecular profiling in non-small cell lung carcinoma.
abstract: Although tumor molecular-profile-directed therapy appears promising in early clinical studies, there are many practical challenges to its successful clinical application in non-small-cell lung cancer (NSCLC). These challenges may be broadly classified as those relating to tumor (heterogeneity), tissue (acquisition and processing), testing (assays for molecular profiling) and trials (clinical evaluation of molecular markers and drugs). Strategies to overcome these challenges include (i) understanding the biological basis of tumor heterogeneity and of carcinogenesis in the large subset of patients with no currently evident driver events; (ii) technological advances in minimally invasive acquisition of tumor and next-generation sequencing (NGS) which would enable single-platform analysis of molecular alterations in limited tissue at a reasonable turnaround time (TAT); (iii) deliberation in early stages of drug development as well as clinical trial design to identify, validate and assess the clinical utility of biomarkers in conjunction with drugs and (iv) collaboration to improve understanding of and accrual to trials enrolling patients with rare molecular alterations.
authors.affiliation: Medical Oncology Branch, National Cancer Institute, Bethesda, 20892, USA.
authors.forename: A
authors.initials: A
authors.lastname: Thomas
authors.forename: A
authors.initials: A
authors.lastname: Rajan
authors.forename: A
authors.initials: A
authors.lastname: Lopez-Chavez
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: G
authors.initials: G
authors.lastname: Giaccone
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D002986:Clinical Trials as Topic; D004252:DNA Mutational Analysis; D020869:Gene Expression Profiling; D006801:Humans; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D020543:Proteome