title: Kinomic profiling of electromagnetic navigational bronchoscopy specimens: a new approach for personalized medicine.
abstract: OBJECTIVE
  Researchers are currently seeking relevant lung cancer biomarkers in order to make informed decisions regarding therapeutic selection for patients in so-called "precision medicine." However, there are challenges to obtaining adequate lung cancer tissue for molecular analyses. Furthermore, current molecular testing of tumors at the genomic or transcriptomic level are very indirect measures of biological response to a drug, particularly for small molecule inhibitors that target kinases. Kinase activity profiling is therefore theorized to be more reflective of in vivo biology than many current molecular analysis techniques. As a result, this study seeks to prove the feasibility of combining a novel minimally invasive biopsy technique that expands the number of lesions amenable for biopsy with subsequent ex vivo kinase activity analysis.
  
  
  METHODS
  Eight patients with lung lesions of varying location and size were biopsied using the novel electromagnetic navigational bronchoscopy (ENB) technique. Basal kinase activity (kinomic) profiles and ex vivo interrogation of samples in combination with tyrosine kinase inhibitors erlotinib, crizotinib, and lapatinib were performed by PamStation 12 microarray analysis.
  
  
  RESULTS
  Kinomic profiling qualitatively identified patient specific kinase activity profiles as well as patient and drug specific changes in kinase activity profiles following exposure to inhibitor. Thus, the study has verified the feasibility of ENB as a method for obtaining tissue in adequate quantities for kinomic analysis and has demonstrated the possible use of this tissue acquisition and analysis technique as a method for future study of lung cancer biomarkers.
  
  
  CONCLUSIONS
  We demonstrate the feasibility of using ENB-derived biopsies to perform kinase activity assessment in lung cancer patients.
authors.affiliation: The Department of Radiation Oncology, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Anderson
authors.affiliation: The Department of Surgery, Division of Cardiothoracic Surgery, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Minnich
authors.affiliation: The Department of Radiation Oncology, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: M Christian
authors.initials: MC
authors.lastname: Dobelbower
authors.affiliation: The Department of Radiation Oncology, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Denton
authors.affiliation: The Department of Pathology, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Alex M
authors.initials: AM
authors.lastname: Dussaq
authors.affiliation: The Department of Radiation Oncology, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Ashley N
authors.initials: AN
authors.lastname: Gilbert
authors.affiliation: The Department of Radiation Oncology, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Rohrbach
authors.affiliation: The Department of Pathology, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Waleed
authors.initials: W
authors.lastname: Arafat
authors.affiliation: The University of Alexandria, Alexandria, Egypt.
authors.forename: Karim
authors.initials: K
authors.lastname: Welaya
authors.affiliation: The Department of Radiation Oncology, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: James A
authors.initials: JA
authors.lastname: Bonner
authors.affiliation: The Department of Radiation Oncology, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Willey
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001999:Bronchoscopy / Q000379:methods*; D000077547:Crizotinib; D055590:Electromagnetic Phenomena; D000069347:Erlotinib Hydrochloride; D005260:Female; D020869:Gene Expression Profiling / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D000077341:Lapatinib; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010770:Phosphotransferases / Q000378:metabolism*; D057285:Precision Medicine / Q000379:methods; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology
chemical_list: D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D011799:Quinazolines; D000077341:Lapatinib; D000077547:Crizotinib; D000069347:Erlotinib Hydrochloride; D010770:Phosphotransferases