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: 10674758
• 负责人: SHAN X. WANG
• 金额: $ 54.69万
• 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/10674758
• 关键词: Adoption; BRAF gene; Biological Assay; Biopsy; Blood; Blood Tests; Blood specimen; Cancer Patient; Clinical; Detection; Disease; Disease Progression; Epidermal Growth Factor Receptor; Exons; 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; cancer type; chemotherapy; cohort; cost effective; detection assay; experience; follow-up; fusion gene; improved; inhibitor therapy; innovation; liquid biopsy; mutant; mutation assay; nanosensors; prognostic; radiological imaging; resistance mechanism; resistance mutation; response; sarcoma; targeted cancer therapy; targeted treatment; therapy resistant; treatment response; 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.]

项目概要/摘要 非小细胞肺癌（NSCLC）的靶向治疗大大改善了患者的预后 然而，与传统化疗相比，据估计高达 20% 的肺癌患者接受了化疗。 EGFR 突变分析之前的一线治疗，需要快速且廉价的基于血液的治疗 循环肿瘤 (ct) DNA 测试可用于有效的治疗选择。此外，ctDNA 可用于重新活检和治疗。 我们已经成功开发了一种高度监测治疗反应或获得性治疗耐药性的方法。 用于检测肺癌“热点”突变组的多重磁纳米传感器测定[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 磁纳米传感器测定的准确性以及与扩展临床结果的相关性 我们追求我们的磁纳米传感器检测可以检测“热点”EGFR 突变 Exon19。 此外，L858R 和 T790M 缺失在大量 NSCLC 患者中具有高敏感性和特异性。 该测定非常适合预后和治疗反应监测，随访 2 周抽血。 开始 TKI 治疗后可以高度预测无进展生存期。 可以使用磁纳米传感器检测的频繁测试（每 2-3 个月一次）来代替射线照相 如果患者保持良好的反应，则进行成像，并且磁纳米传感器测定可以检测到 成像前疾病的进展。 2) 在磁纳米传感器阵列上开发广泛的 ctDNA 突变面板检测 [用于 NSCLC 治疗 选择、监测和预后。]我们勇敢地说，我们之前开发的 EGFR ctDNA 磁- 纳米传感器突变检测可进一步扩展到包括与第三代 TKI 相关的突变 耐药机制和其他基因突变，以更好地帮助非小细胞肺癌[治疗选择、监测、 ] 为此，我们的目标是开发一个 ctDNA 突变面板，帮助确定治疗方案 对于NSCLC患者，不仅包括EGFR突变，还包括KRAS、BRAF V600E、ALK-EML4融合等 [我们的目标是在整个治疗过程中监测患者的反应性和预后。] 该项目的预期成果是 ctDNA EGFR 磁纳米传感器测定的临床验证， 扩展和复用现有的 EGFR 检测，包括 KRAS、BRAF V600E、ALK-EML4 融合，以及 ROS1 融合，并利用该测定[进行有效的治疗选择、预后和/或反应监测。]

项目成果

Real-time temperature correction for magnetoresistive biosensors integrated with temperature modulator.

与温度调制器集成的磁阻生物传感器的实时温度校正。

• DOI: 10.1016/j.biosx.2023.100356
• 发表时间: 2023
• 期刊: Biosensors & bioelectronics: X
• 作者: Kim,Songeun;Wang,ShanX;Lee,Jung-Rok
• 通讯作者: Lee,Jung-Rok

Longitudinal analysis of anti-SARS-CoV-2 neutralizing antibody (NAb) titers in vaccinees using a novel giant magnetoresistive (GMR) assay.

• DOI: 10.1016/j.snb.2023.133773
• 发表时间: 2023-07-15
• 期刊: SENSORS AND ACTUATORS B-CHEMICAL
• 影响因子: 8.4
• 作者: Ng, Elaine;Choi, Christopher;Wang, Shan X.
• 通讯作者: Wang, Shan X.

Magnetic supercluster particles for highly sensitive magnetic biosensing of proteins.

• DOI: 10.1007/s00604-022-05354-x
• 发表时间: 2022-06-14
• 期刊: MICROCHIMICA ACTA
• 影响因子: 5.7
• 作者: Kim, Songeun;Kim, Junyoung;Im, Jisoo;Kim, Minah;Kim, Taehyeong;Wang, Shan X.;Kim, Dokyoon;Lee, Jung-Rok
• 通讯作者: Lee, Jung-Rok