Rapid and affordable magneto-nanosensors for ctDNA-guided lung cancer management

用于 ctDNA 引导肺癌管理的快速且经济实惠的磁纳米传感器

• 批准号: 10304404
• 负责人: SHAN X. WANG
• 金额: $ 57.35万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-02 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10304404
• 关键词: Adoption; BRAF gene; Biological Assay; Blood; Blood Tests; Blood specimen; Cancer Patient; Clinical; Detection; Diagnostic radiologic examination; Disease; Disease Progression; Epidermal Growth Factor Receptor; Gene Fusion; Generations; Genes; Goals; Hot Spot; Image; Magnetic nanoparticles; Malignant neoplasm of lung; Monitor; Mutation; Mutation Analysis; Non-Small-Cell Lung Carcinoma; Outcome; Patient Monitoring; Patient imaging; Patient-Focused Outcomes; Patients; Pilot Projects; Plasma; Prior Therapy; Prognosis; Progression-Free Survivals; ROS1 gene; Rattus; Sampling; Selection for Treatments; Sensitivity and Specificity; Specificity; Testing; Time; Translating; Tyrosine Kinase Inhibitor; Validation; actionable mutation; base; cancer type; chemotherapy; cohort; cost effective; detection assay; experience; follow-up; fusion gene; improved; innovation; liquid biopsy; mutant; mutation assay; nanosensors; prognostic; resistance mechanism; resistance mutation; response; sarcoma; targeted cancer therapy; targeted treatment; therapy resistant; tumor DNA

Project Summary / Abstract Targeted therapy for the treatment of non-small cell lung cancer (NSCLC) has greatly improved patient outcomes compared to traditional chemotherapy. However, it is estimated that up to 20% of lung cancer patients receive first-line therapy prior to EGFR mutational analysis, necessitating the need for a rapid and cheap blood-based circulating tumor (ct) DNA test for efficient therapy selection. Additionally, ctDNA can be useful for rebiopsy and monitoring of response to therapy or acquired resistance to therapy. We have successfully developed a highly multiplexable magneto-nanosensor assay for the detection of “hot spot” mutation panel for lung cancer [targeted therapy selection or therapy monitoring and prognosis.] Specific aims of the project are: 1) Validate ctDNA EGFR magneto-nanosensor assay accuracy and correlations to clinical outcome on expanded cohort. We hypothesize that our magneto-nanosensor assay can detect “hot spot” EGFR mutations Exon19 deletion, L858R, and T790M with high sensitivity and specificity in a large cohort of NSCLC patients. Additionally, this assay can be well suited for prognosis and therapy response monitoring. A follow-up blood draw 2 weeks after initiating TKI therapy can be highly predictive of progression free survival. Additionally, we hypothesize that frequent testing (every 2-3 months) on the magneto-nanosensor assay could be used in lieu of radiographic imaging if patient maintains favorable response, and that the magneto-nanosensor assay could detect progression of disease prior to imaging. 2) Develop an extensive ctDNA mutation panel assay on magneto-nanosensor arrays [for NSCLC treatment selection, monitoring, and prognosis.] We hypothesize that our previously developed EGFR ctDNA magneto- nanosensor mutation assay can be further expanded to include mutations relevant to third-generation TKI resistance mechanisms and mutations in other genes to better aid in NSCLC [treatment selection, monitoring, and prognosis.] In this aim, our goal is to develop a ctDNA mutation panel that can help identify treatment options for NSCLC patients, not only EGFR mutations but also including KRAS, BRAF V600E, ALK-EML4 fusions, and ROS1 fusions. [We aim to monitor patients throughout their treatment course for responsiveness and prognosis.] The expected outcomes of this project are clinical validation of a ctDNA EGFR magneto-nanosensor assay, expanding and multiplexing the existing EGFR assay to include KRAS, BRAF V600E, ALK-EML4 fusions, and ROS1 fusions, and utilizing the assay [for efficient therapy selection, prognosis, and/or response monitoring.]

项目摘要/摘要 靶向治疗非小细胞肺癌(NSCLC)极大地改善了患者的预后 与传统的化疗相比。然而，据估计，多达20%的肺癌患者接受了 在EGFR突变分析之前的一线治疗，需要快速和廉价的基于血液的 循环肿瘤(Ct)dna检测用于有效治疗选择。此外，ctDNA可用于再活组织检查和 监测治疗反应或对治疗的获得性抵抗。我们已经成功地开发出了一种高度 多路磁纳米传感器检测肺癌“热点”突变面板[靶向 治疗选择或治疗监测和预后。] 该项目的具体目标是： 1)验证ctDNA EGFR磁纳传感器检测的准确性及其与临床结果的相关性。 一群人。我们假设我们的磁性纳米传感器检测方法可以检测到“热点”的egfr基因突变外显子19。 缺失、L858R和T790M在大量非小细胞肺癌患者中具有较高的敏感性和特异性。另外， 该检测方法可用于预后监测和治疗反应监测。随访2周采血一次 在开始TKI治疗后，TKI治疗可以高度预测无进展生存率。此外，我们假设 磁性纳米传感器检测的频繁测试(每2-3个月)可以用来代替射线照相。 如果患者保持良好的反应，成像，磁纳米传感器测试可以检测到 成像前的疾病进展情况。 2)在磁性纳米传感器阵列上开发一种广泛的ctdna突变面板分析[用于非小细胞肺癌治疗]。 选择、监测和预后。]我们假设我们之前开发的EGFR ctDNA磁电机- 纳米传感器突变检测可以进一步扩大到包括与第三代TKI相关的突变 耐药机制和其他基因的突变，以更好地帮助非小细胞肺癌[治疗选择，监测， 和预后。]在这个目标中，我们的目标是开发一个ctdna突变小组，它可以帮助确定治疗方案。 对于NSCLC患者，不仅EGFR突变，而且包括KRAS、BRAF V600E、ALK-EML4融合和 ROS1融合。[我们的目标是监测患者在整个治疗过程中的反应性和预后。] 该项目的预期结果是ctDNA EGFR磁纳米传感器检测的临床验证， 扩展和复用现有的EGFR检测，以包括KRAS、BRAF V600E、ALK-EML4融合和 ROS1融合，并利用该检测[用于有效的治疗选择、预后和/或反应监测。]