title: Emerging Biomarkers in Personalized Therapy of Lung Cancer.
abstract: The two clinically validated and Food and Drug Administration approved lung cancer predictive biomarkers (epidermal growth factor receptor mutations and anaplastic lymphoma kinase (ALK) translocations) occur in only about 20 % of lung adenocarcinomas and acquired resistance develops to first generation drugs. Several other oncogenic drivers for lung adenocarcinoma have emerged as potentially druggable targets with new predictive biomarkers. Oncologists are requesting testing for ROS1 translocations which predict susceptibility to crizotinib, already approved for ALK positive lung cancers. Other potential biomarkers which are currently undergoing clinical trials are RET, MET, HER2 and BRAF. Detection of these biomarkers includes fluorescent in situ hybridization and/or reverse transcriptase polymerase chain reaction (ROS1, RET, HER2), mutation analysis (BRAF) and immunohistochemistry (MET). Screening by immunohistochemistry may be useful for some biomarkers (ROS1, BRAF). Targeted next generation sequencing techniques may be useful as well. These five biomarkers are under consideration for inclusion in revised lung cancer biomarker guidelines by the College of American Pathologists, International Association for the Study of Lung Cancer and Association for Molecular Pathology.
authors.affiliation: Houston Methodist Hospital, Weill Medical College of Cornell University, Houston, TX, USA. pcagle@houstonmethodist.org.
authors.forename: Philip T
authors.initials: PT
authors.lastname: Cagle
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA. kraparia@northwestern.edu.
authors.forename: Kirtee
authors.initials: K
authors.lastname: Raparia
authors.affiliation: Houston Methodist Hospital, Houston, TX, USA. bpportier@houstonmethodist.org.
authors.forename: Bryce P
authors.initials: BP
authors.lastname: Portier
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D048493:Proto-Oncogene Proteins B-raf; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; C000626173:ALK protein, human; C508053:ERBB2 protein, human; C099282:RET protein, human; C062333:ROS1 protein, human; C482119:BRAF protein, human
keywords: BRAF; Crizotinib; Fluorescent in situ hybridization; HER2; Immunohistochemistry; MET; Multikinase inhibitors; RET; ROS1; Reverse transcriptase polymerase chain reaction