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

对癌症不断发展的认识表明，每一种肿瘤都有不同的特征，这是由疾病的分子病理学驱动的。根据这种异质性预测，靶向治疗药物比“一刀切”的方法要成功得多。目前，除了活检，没有其他工具来分析实体组织肿瘤细胞的耐药性。这一限制不包括对治疗过程中出现的分子标记的检测。本项目的目标是开发和表征基于CTC的分子耐药测试，并在临床样品中应用。15-20%的非小细胞肺癌是由表皮生长因子受体（EGFR）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T790M突变引起的。目前，耐药性在医学上是通过肿瘤进展来确定的。作为一种替代方法，提取释放到血液中的少量循环肿瘤细胞（CTC）以检测T790M突变的出现，为实时对患者特异性肿瘤细胞进行基因分型提供了一种策略。这将产生一种根本性的技术，用于个性化医疗中的预测癌症测试。

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.