Lung cancer : journal of the International Association for the Study of Lung Cancer
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Multicenter Study
Phase II trial of customized first line chemotherapy according to ERCC1 and RRM1 SNPs in patients with advanced non-small-cell lung cancer.
Customized chemotherapy has several advantages: patients are more likely to be treated with the most effective agents and can be spared the toxicity of ineffective drugs. Based on the literature, excision repair cross complementation group 1 (ERCC1) and ribonucleotide reductase M1 (RRM1) genes represent predictive biomarkers of response to platinum compound and gemcitabine, in NSCLC. ⋯ We observed an increase of ORR in NSCLC patients when they were treated with chemotherapy according to ERCC1 and RRM1 SNPs status.
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Although T790M mutation is considered to be the major mechanism of acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC), its clinical implication remains undetermined. ⋯ The identification of T790M as acquired resistance mechanism was clinically feasible. Although T790M had no prognostic or predictive role in the present study, further research is necessary to identify patients with T790M-mutant tumors who might benefit from newly developed T790M-specific TKIs.
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P276-00 is a novel cyclin-dependent kinase (CDK) inhibitor is in Phase II clinical trials. Valproic acid (VPA), an antiepileptic agent has been associated with anticancer activity, through the inhibition of histone deacetylase I. Here we investigate the effect of the combination of VPA and P276-00, in non-small-cell lung cancer (NSCLC) cell lines. ⋯ This study indicates that the combination of HDAC inhibitor VPA with CDK inhibitor P276-00 is promising novel molecularly targeted therapeutic approach for NSCLC treatment.