title: In Vitro Drug Sensitivity Tests to Predict Molecular Target Drug Responses in Surgically Resected Lung Cancer.
abstract: BACKGROUND
  Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and anaplastic lymphoma kinase (ALK) inhibitors have dramatically changed the strategy of medical treatment of lung cancer. Patients should be screened for the presence of the EGFR mutation or echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene prior to chemotherapy to predict their clinical response. The succinate dehydrogenase inhibition (SDI) test and collagen gel droplet embedded culture drug sensitivity test (CD-DST) are established in vitro drug sensitivity tests, which may predict the sensitivity of patients to cytotoxic anticancer drugs. We applied in vitro drug sensitivity tests for cyclopedic prediction of clinical responses to different molecular targeting drugs.
  
  
  METHODS
  The growth inhibitory effects of erlotinib and crizotinib were confirmed for lung cancer cell lines using SDI and CD-DST. The sensitivity of 35 cases of surgically resected lung cancer to erlotinib was examined using SDI or CD-DST, and compared with EGFR mutation status.
  
  
  RESULTS
  HCC827 (Exon19: E746-A750 del) and H3122 (EML4-ALK) cells were inhibited by lower concentrations of erlotinib and crizotinib, respectively than A549, H460, and H1975 (L858R+T790M) cells were. The viability of the surgically resected lung cancer was 60.0 ± 9.8 and 86.8 ± 13.9% in EGFR-mutants vs. wild types in the SDI (p = 0.0003). The cell viability was 33.5 ± 21.2 and 79.0 ± 18.6% in EGFR mutants vs. wild-type cases (p = 0.026) in CD-DST.
  
  
  CONCLUSIONS
  In vitro drug sensitivity evaluated by either SDI or CD-DST correlated with EGFR gene status. Therefore, SDI and CD-DST may be useful predictors of potential clinical responses to the molecular anticancer drugs, cyclopedically.
authors.affiliation: Division of Thoracic Surgery, Department of Surgery II, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Miyazaki
authors.affiliation: Division of Thoracic Surgery, Department of Surgery II, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Anayama
authors.affiliation: Division of Thoracic Surgery, Department of Surgery II, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hirohashi
authors.affiliation: Division of Thoracic Surgery, Department of Surgery II, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Okada
authors.affiliation: Division of Thoracic Surgery, Department of Surgery II, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.
authors.forename: Motohiko
authors.initials: M
authors.lastname: Kume
authors.affiliation: Division of Thoracic Surgery, Department of Surgery II, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Orihashi
mesh_terms: D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D000077547:Crizotinib; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics*; D066246:ErbB Receptors; D000069347:Erlotinib Hydrochloride / Q000494:pharmacology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009154:Mutation / Q000187:drug effects / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D008869:Microtubule-Associated Proteins; D015514:Oncogene Proteins, Fusion; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; D000069347:Erlotinib Hydrochloride; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases