Kinomic profiling of electromagnetic navigational bronchoscopy specimens: a new approach for personalized medicine

PLoS One. 2014 Dec 30;9(12):e116388. doi: 10.1371/journal.pone.0116388. eCollection 2014.

Abstract

Purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bronchoscopy / methods*
  • Crizotinib
  • Electromagnetic Phenomena
  • Erlotinib Hydrochloride
  • Female
  • Gene Expression Profiling / instrumentation
  • Gene Expression Profiling / methods*
  • Humans
  • Lapatinib
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Phosphotransferases / metabolism*
  • Precision Medicine / methods
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrazoles / pharmacology
  • Pyridines / pharmacology
  • Quinazolines / pharmacology

Substances

  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • Quinazolines
  • Lapatinib
  • Crizotinib
  • Erlotinib Hydrochloride
  • Phosphotransferases

Grant support

This work was supported by The Department of Radiation Oncology Intramural Pilot Research Program, The University of Alabama at Birmingham (to MCD), and also by the Egyptian Partnership and Ownership initiative (PAR-OWN) international research fellowship (to KW), http://www.estp.sci.eg/english/national_initiatives/mobility_grants/parown. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.