基于核酸适配体的循环肿瘤细胞实时克隆分型指导非小细胞肺癌EGFR-TKI药物二次应用的探索性研究

项目名称： 基于核酸适配体的循环肿瘤细胞实时克隆分型指导非小细胞肺癌EGFR-TKI药物二次应用的探索性研究

项目编号： No.81472186

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 汤传昊

作者单位： 中国人民解放军军事科学院军事医学研究院

项目金额： 72万元

中文摘要： 尽管EGFR-TKI在NSCLC患者中疗效显著，但患者耐药后的治疗选择非常有限。我们前期的临床研究发现， EGFR-TKI的二次应用是耐药患者可行的治疗方案之一，而EGFR-TKI敏感型CTC的动态变化将有助于指导其合理应用。我们前期与中科院化学所的合作研究显示，核酸适配体不仅可以有效富集NSCLC患者的CTC，还可将CTC区分为不同的克隆亚型。在本课题中，我们拟与中科院化学所继续深入合作，通过Cell-SELEX技术筛选分别与EGFR-TKI敏感细胞及耐药细胞特异结合的核酸适配体组合，体外验证其功能，进而将其用于EGFR-TKI二次治疗患者外周血的检测，分析EGFR-TKI敏感型CTC的动态变化与该药物疗效的相关性，为其合理的二次应用提供准确可靠的生物标记物。本研究对EGFR-TKI以外药物的合理使用也有借鉴作用，有助于更好的实现肿瘤患者的个体化治疗，具有良好的应用前景和学术价值。

中文关键词： C05_气管；支气管；肺肿瘤；循环肿瘤细胞；核酸适配体；表皮生长因子受体；酪氨酸激酶抑制剂

英文摘要： Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have evident effect in non-small-cell lung cancer (NSCLC) patients. However, most of the patients will eventually undergo progressive disease (PD) despite the initial response, and once PD was happened, the available treatment options of those patients became very narrow. We have reported previously that retreatment of EGFR-TKI can be considered as an option for those patients, and the dynamic changing of circulating tumor cell (CTC) which is sensitive to EGFR-TKI may provide assistance in rational re-administration of EGFR-TKI. Cooperating with the institute of chemistry, Chinese academy of sciences, we have found in our previous research that DNA aptamers could not only effectively enrich CTCs of NSCLC patients, but also recognize the subtypes of those cells. In this research, we will continue our cooperation. Using Cell-SELEX method, we are trying to select the DNA aptamers which could specifically recognize EGFR-TKI sensitive cells and resistant cells, respectively. After its function was verified in vitro, the selected DNA aptamers would be used in the CTC test of patients who received EGFR-TKI retreatment. We believe that the correlation analysis of the dynamic changing in EGFR-TKI sensitive CTC between curative effects of EGFR-TKI would provide reliable biomarker for the rational re-administration of EGFR-TKI. Meanwhile, our research is applicable for other drugs that beyond EGFR-TKI. Our research could help the physicians to fulfill better the individualized treatment to cancer patients and have good prospect in clinical application and academic value.

英文关键词： Non-Small-Cell Lung Cancer;Circulating Tumor Cell;DNA Aptamer;Epidermal Growth Factor Receptor;Tyrosine Kinase Inhibitor