TAS::75 0849::TAS SBIR TOPIC 277 - NOVEL CTC-BASED TEST FOR LUNG CANCER DRUG RES

对癌症不断发展的理解表明，每种肿瘤都具有由疾病的分子病理学驱动的独特特征。通过这种异质性预测，靶向治疗剂比"一刀切“的方法要成功得多。目前，除了活检之外，没有工具来分析实体组织肿瘤细胞中的抗性。该限制排除了治疗期间出现的分子标志物检测。本项目的目标是开发和表征基于CTC的分子耐药性测试，并展示其在临床样品中的应用。15-20%的非小细胞肺癌是由表皮生长因子受体（EGFR）中的激活突变驱动的，这种突变可以用EGFR抑制剂如吉非替尼或厄洛替尼非常有效地治疗。对这些药物的耐药性普遍存在;一半的时间是由T790 M突变引起的。目前，耐药性在医学上通过证明肿瘤进展来确定。作为一种替代方法，提取释放到血流中的少量循环肿瘤细胞（CTC）用于检测T790 M突变的出现，提供了一种真实的时间对患者特异性肿瘤细胞进行基因分型的策略。这将为个性化医疗中的预测性癌症测试提供一种根本性的技术。

The evolving understanding of cancer indicates every tumor has distinct characteristics driven by the molecular pathology of the disease. Predicted by this heterogeneity, targeted therapeutic agents are much more successful than a ¿one size fits all¿ approach. Currently, there are no tools to analyze resistance in solid tissue tumor cells other than biopsy. This limitation excludes test for molecular markers that emerge during treatment. The goal of this project is to develop and characterize a CTC based molecular drug resistance test and demonstrate application in clinical samples. 15-20% of non-small cell lung cancers are driven by activating mutations in the epidermal growth factor receptor (EGFR), a mutation that can be very effectively treated with EGFR inhibitors such as gefitinib or erlotinib. Resistance to these drugs arises universally; caused half of the time by a T790M mutation. Currently, resistance is determined medically by demonstrating tumor progression. As an alternative approach, extracting the small numbers of circulating tumor cells (CTC) released into the bloodstream for detection of the emergence of the T790M mutation offers a strategy for genotyping patient-specific tumor cells in real time. This will produce a fundamentally enabling technology for predictive cancer tests in personalized medicine.