IGF::OT::IGF R&D BIOMEDICAL RESEARCH

IGF::OT::IGF R

• 批准号: 9356697
• 负责人: CASTRO LAICER
• 金额: $ 29.97万
• 依托单位: GINER, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-19 至 2017-03-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9356697
• 关键词: Accounting; Address; Alternative Therapies; Biological Markers; Biomedical Research; Biosensor; Blood; Blood specimen; DNA; Detection; Disease; Drug resistance; Epidermal Growth Factor; FDA approved; Human; Measures; Mediating; Methods; Mutation; Mutation Detection; Physiological; Recurrent disease; Resistance; Sampling; Serum; Techniques; Time; Training; Treatment outcome; base; cancer therapy; circulating DNA; cost; design; digital; liquid biopsy; prototype; research and development; sensor; targeted treatment; tumor DNA

The availability of liquid biopsies, such as sampling of blood to measure key disease biomarkers, could aid in the detection of blood-circulating tumor DNA (ctDNA) known to confer resistance to cancer therapy. For example, the T790M mutation in the epidermal growth factor (EGFR) accounts for 50% of acquired resistance to FDA-approved EGFR targeted therapies. Detection of this mutation is important to evaluate disease relapse and guide the selection of alternative therapies for better treatment outcome. Therefore, identification of ctDNAs that harbor EGFR-specific drug resistant mutations needs to be noninvasive. However, detection of ctDNAs is challenging because they constitute a small fraction of the total number of normal circulating DNA in blood. Current detection methods rely on digital PCR-based techniques, which are limited because of high cost, need for highly trained operators, requirement for time-consuming sample purification steps, slow sample-to-answer time, and limited ability for parallel analysis of a large number of biomarkers. To address this need, Giner, Inc. proposes to develop an electrochemical biosensor for multiplexed detection of ctDNA biomarkers associated with acquired resistance to EGFR-targeted therapies. This sensor will be designed to achieve both selective and sensitive detection of ctDNA in human serum at physiological relevant concentrations.

液体活检的可用性，例如血液采样以测量关键疾病生物标志物，可以帮助检测已知赋予癌症治疗抗性的血液循环肿瘤DNA（ctDNA）。例如，表皮生长因子（EGFR）中的T790M突变占FDA批准的EGFR靶向治疗获得性耐药的50%。这种突变的检测对于评估疾病复发和指导选择替代疗法以获得更好的治疗结果非常重要。因此，携带EGFR特异性耐药突变的ctDNA的鉴定需要是非侵入性的。然而，ctDNA的检测是具有挑战性的，因为它们构成血液中正常循环DNA总数的一小部分。目前的检测方法依赖于基于数字PCR的技术，其由于高成本、需要高度训练的操作员、需要耗时的样品纯化步骤、缓慢的样品应答时间以及并行分析大量生物标志物的能力有限而受到限制。为了解决这一需求，Giner，Inc.提出开发一种电化学生物传感器，用于多重检测与EGFR靶向治疗获得性抗性相关的ctDNA生物标志物。该传感器将被设计为在20 ℃下实现人血清中ctDNA的选择性和灵敏性检测。 生理相关浓度。