Research on Molecular Therapeutic Targets and Biomarkers for the Diagnosis and Stratification in Lung Cancer

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The aim of this research is to identify molecular therapeutic targets and Biomarkers for the diagnosis and stratification in lung cancer.We searched for genes specifically overexpressed in lung cancer through microarray analysis, and identified seven genes, including AKRB1B10, in squamous cell carcinoma (SCC) of the lung. AKR1B10 was overexpressed in most cases with SCC, which is closely associated with smoking, and in many adenocarcinomas from smokers. These results suggest that AKR1B10 is a potential diagnostic marker specific to smokers' non-small cell lung cancers (NSCLCs) and might be involved in tobacco-related carcinogenesis.We next studied on the biomarker in molecular targeting therapy using EGF receptor (EGFR)-tyrosine kinase inhibitors (TKIs). Retrospective analyses have shown that activating mutations in exons 18-21 of the EGFR gene are a predictor of response to EGFR-TKIs. We conducted a phase II study to evaluate the efficacy and safety of gefitinib, one of EGFR-TKIs, as first-line therapy for advanced NSCLCs with EGFR mutations. For mutation analysis, DNA was extracted from paraffin-embedded tissues and EGFR mutations were analysed by direct sequence of PCR products. Twenty (24%) of the 82 patients analysed had EGFR mutations. Sixteen patients were enrolled and treated with gefitinib. Twelve patients had objective response and response rate was 75%. This study has shown that mutations (deletions in exon 19 and L858R point mutation in exon 21) of the EGFR gene are a predictor of response to EGFR-TKIs.