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

基本信息

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
项目类别：
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

项目摘要

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 /摘要用于治疗非小细胞肺癌（NSCLC）的靶向疗法已大大改善了患者的预后与传统的化学疗法相比，据估计，多达20％的肺癌患者 EGFR变异分析之前的一线疗法，必须需要快速，廉价的循环肿瘤（CT）DNA测试进行有效的治疗。监测对治疗的反应或对治疗的抗药性。多重磁纳米传感器测定用于检测肺癌的“热点”突变面板[靶向治疗选择或治疗监测和程序病。] 该项目的具体目标是： 1）验证ctDNA EGFR磁纳米传感器关联和扩展的临床结果的腐蚀同类。我们假设我们的磁纳米传感器测定可以检测到“热点” 在大量NSCLC患者中，删除，L858R和T790M具有高灵敏度和特异性。这赛季非常适合预后和治疗反应监测2周。启动TKI治疗可以高度预测无进展的生存可以使用射线传感器测定的频繁测试（每2-3个月一次）可以代替射线照相成像如果患者保持有利的呼吸，并且磁纳米传感器测定可能成像之前的疾病进展。 2）在磁纳米传感器阵列上开发广泛的CTDNA突变面板测定法[用于NSCLC处理我们假设我们先前开发的EGFR CTDNA磁铁 - 纳米传感器突变测定可以进一步扩展，包括与第三代TKI相关的突变其他基因中的抗性机制和突变，以更好地帮助NSCLC [治疗选择，监测， [和预后。]在此目标中，我们的目标是开发一个可以帮助识别治疗选择的ctDNA突变面板对于NSCLC患者，而不是ONLS EGFR突变，而是包括KRAS，BRAF V600E，ALK-EML4融合，以及 ROS1融合。该项目的预期结果是CTDNA EGFR磁纳米传感器测定法的临床验证，扩展和多路复用现有，包括KRAS，BRAF V600E，ALK-EML4融合，以及 ROS1融合，并利用该测定法[用于选择，程序病和/或反应监测。]