循环肿瘤细胞实时分子分型指导乳腺癌HER2靶向药物合理使用的探索性研究

项目名称： 循环肿瘤细胞实时分子分型指导乳腺癌HER2靶向药物合理使用的探索性研究

项目编号： No.81472477

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： 江泽飞

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： 52万元

中文摘要： HER2靶向药物是HER2阳性乳腺癌患者最重要的治疗手段之一，然而由于无法实时、动态的获得满足检测要求的肿瘤标本，严重影响了该类药物的合理有效使用。我们在前期的研究中发现，CTC检测可以克服肿瘤组织在动态检测方面的不足，更精确的指导患者的个体化治疗。在本课题中，我们拟借助新一代的CTC微流控纳米芯片检测平台，结合本单位的优势患者资源及本课题组即将和正在承担的大型临床试验，动态、实时的获得数量、质量满足要求的CTC样品，通过CTC的实时分子分型，为HER2靶向药物的合理使用提供准确可靠的疗效预测和评价。同时通过耐药患者CTC的分子分型及全基因组分析，探索现有HER2靶向药物的耐药机制，为患者后续的用药选择和药物研发提供重要依据。本研究可以解决HER2靶向药物合理使用所面临的样品来源问题，有助于更好的实现患者的个体化治疗，未来的研究成果也可推广至其他药物，具有重要的学术价值和良好的应用前景。

中文关键词： C21_乳腺肿瘤；循环肿瘤细胞；分子分型；人表皮生长因子受体2；靶向药物

英文摘要： Human Epidermal growth factor receptor 2(HER2) target drugs are one of the most important therapies for HER2 positive breast cancer patients. However, the rational administration of these drugs was greatly hampered by the difficulties in real-time sampling of the tumor tissue. We have reported in our previous research that the detection of circulating tumor cell (CTC) may avoid the shortcomings of tumor tissue and provide assistant in accurate management of the individual therapy to the patients. In this research, based on the resources advantages of our hospital in breast cancer and the large clinical trial that we are going to undertake, we plan to use the microfluidic Nano-Velcro Chip, a new platform for CTC detection, to obtain quantified and qualified CTC sample real-timely. The molecular analysis of these CTC sample will provide accurate prognosis and therapeutic evaluation to the patients. Meanwhile, for patients who resistant to HER2 target therapy, molecular analysis and whole genomic sequencing of CTC will be carry out to explore the resistance mechanism, which will provide important reference for the subsequent drug selection and drug development. Our research will settle the sampling problem that faced in rational administration of HER2 target drugs. Meanwhile, our research is applicable for other drugs, it could help the physicians to fulfill better the individualized treatment to breast cancer patients and have good prospect in clinical application and academic value.

英文关键词： breast cancer;circulating tumor cell;molecular typing;HER2;targeted drugs