Abstract
BackgroundEpidermal 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.MethodsThe 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.ResultsHCC827 (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.ConclusionsIn 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.
Highlights
Lung cancer is the leading cause of cancer-related mortality in many developed countries while adenocarcinoma represents 70% of the cases of non-small cell lung cancer (NSCLC)
HCC827 (Exon19: E746-A750 del) and H3122 (EML4-anaplastic lymphoma kinase (ALK)) cells were inhibited by lower concentrations of erlotinib and crizotinib, respectively than A549, H460, and H1975 (L858R+T790M) cells were
In vitro drug sensitivity evaluated by either succinate dehydrogenase inhibition (SDI) or CD-DST correlated with epidermal growth factor receptor (EGFR) gene status
Summary
Lung cancer is the leading cause of cancer-related mortality in many developed countries while adenocarcinoma represents 70% of the cases of non-small cell lung cancer (NSCLC). In Japanese patients, approximately 50 and 5% of adenocarcinomas have a mutation in the epidermal growth factor receptor (EGFR) [1] and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene, respectively. Molecular target anticancer drugs such as EGFR-tyrosine kinase inhibitors (TKIs) and ALK inhibitors have dramatically changed the strategy of clinical treatment of cancer. EGFR mutation-positive cases do not always exhibit good clinical responses to EGFR TKI therapy. 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. We applied in vitro drug sensitivity tests for cyclopedic prediction of clinical responses to different molecular targeting drugs
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