title: Primary and secondary resistance to tyrosine kinase inhibitors in lung cancer.
abstract: BACKGROUND
  Tyrosine kinase inhibitors (TKI) have emerged as important therapeutic agents for the treatment of several types of cancer including lung cancer. Recent research attempts show that only a small population of cancer patients responds to TKI and furthermore, these patients eventually develop resistance. Studies support the classification of resistance in primary and secondary resistance.
  
  
  METHODS
  In the present study the differentiation between primary and secondary resistance to TKI in lung cancer cell lines was investigated. Lung cancer cell lines were tested for viability, apoptosis and cell cycle after exposure to the TKI erlotinib and gefitinib.
  
  
  RESULTS
  Cells with primary resistance showed similar cell-cycle patterns to those with secondary resistance but differences were observed between the two groups in the viability and apoptosis assays.
  
  
  CONCLUSIONS
  Understanding the effects of TKI on cell signaling pathways would shed light on the mechanisms of acquired resistance and the differences between primary and secondary resistance.
authors.affiliation: Fraunhofer Institut für Zelltherapie und Immunologie, Leipzig, Germany Institut für Pharmazie, Universität Leipzig, Germany jacinta.simasi@izi.fraunhofer.de.
authors.forename: Jacinta
authors.initials: J
authors.lastname: Simasi
authors.affiliation: Fraunhofer Institut für Zelltherapie und Immunologie, Leipzig, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schubert
authors.affiliation: Fraunhofer Institut für Zelltherapie und Immunologie, Leipzig, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Oelkrug
authors.affiliation: Klinik für Lungen- und Bronchialmedizin-Klinikum Kassel, Kassel, Germany.
authors.forename: Adrian
authors.initials: A
authors.lastname: Gillissen
authors.affiliation: Institut für Pharmazie, Universität Leipzig, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Nieber
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D005434:Flow Cytometry; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: Lung cancer; apoptosis; cell cycle; resistance; tyrosine kinase inhibitors