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

肺癌诊断和分层的分子治疗靶点和生物标志物研究

基本信息

批准号：
16390231
负责人：
AKITA Hirotoshi
金额：
$ 8.26万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390231/
关键词：
lung cancer biomarker AKR1B10 EGFR mutation 喫煙扁平上皮癌タバコ発癌

项目摘要

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.

这项研究的目的是确定肺癌诊断和分层的分子治疗靶标和生物标志物。我们通过微阵列分析搜索了在肺癌中特异性过表达的基因，并在鳞状细胞癌（SCC）（SCC）中鉴定了七个基因，包括AKRB1B10，包括AKRB1B10。肺部。在大多数情况下，AKR1B10与吸烟密切相关的SCC以及吸烟者的许多腺癌密切相关。这些结果表明，AKR1B10是吸烟者非小细胞肺癌（NSCLC）特有的潜在诊断标记，并且可能参与了与烟草相关的致癌作用。酪氨酸激酶抑制剂（TKIS）。回顾性分析表明，EGFR基因18-21的外显子中激活突变是对EGFR-TKI的反应的预测指标。我们进行了II期研究，以评估Gefitinib（EGFR-TKIS之一）作为具有EGFR突变的晚期NSCLC的一线治疗。为了进行突变分析，从石蜡包裹的组织中提取DNA，并通过PCR产物的直接序列分析EGFR突变。分析的82名患者中有20名（24％）具有EGFR突变。 16例患者接受了吉非替尼的治疗。十二例患者的客观反应，反应率为75％。这项研究表明，EGFR基因的突变（外显子19和L858R点突变中的缺失）是对EGFR-TKIS响应的预测指标。