Liquid Biopsy for treatment stratification of IDH1.R132H and EGFRvIII mutant gliomas

用于 IDH1.R132H 和 EGFRvIII 突变神经胶质瘤治疗分层的液体活检

• 批准号: 9976485
• 负责人: Bob S Carter
• 金额: $ 80.88万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-22 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9976485
• 关键词: Adoption; Age; Alkylating Agents; Angiogenesis Inhibitors; Area; Biological Assay; Biological Markers; Biometry; Biopsy; Blood; Blood Circulation; Blood Tests; Brain; Brain Neoplasms; Cancer Diagnostics; Caring; Characteristics; Clinical; Clinical Laboratory Improvement Amendments; Collaborations; Conformal Radiotherapy; DNA; Data; Detection; Diagnosis; Diagnostic; Diagnostic tests; Disease; Epidermal Growth Factor Receptor; Excision; General Hospitals; Genes; Glioma; Goals; Gold; Good Clinical Practice; Histology; Human; In Vitro; Industry; Institution; International; Isocitrate Dehydrogenase; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of brain; Massachusetts; Medical Device; Methods; Molecular; Monitor; Morbidity - disease rate; Mutation; Neurosurgeon; Operative Surgical Procedures; Outcome; Parents; Patient Care; Patients; Performance; Pharmacotherapy; Phase; Plasma; Point Mutation; Postoperative Period; Procedures; Process; RNA; Reproducibility; Research; Resources; Risk; Sampling; Sensitivity and Specificity; Source; Specificity; Standardization; Survival Rate; Testing; Therapeutic Intervention; Time; Tissues; Tumor Tissue; Tumor stage; Validation; Variant; Work; awake; base; bevacizumab; cancer cell; cancer type; clinical care; clinical practice; cohort; cost; cross reactivity; diagnostic assay; digital; effective therapy; exosome; extracellular; extracellular vesicles; follow-up; high risk; image guided; improved; innovative technologies; liquid biopsy; member; minimally invasive; mortality; multidisciplinary; mutant; mutation assay; neurosurgery; novel; outcome forecast; patient stratification; personalized care; personalized medicine; prospective; success; temozolomide; treatment stratification; tumor; virtual; young adult

Project​ ​Summary Extracellular vesicles (EVs) and cell free DNA have emerged as a promising surrogate for the tissue biopsy, potentially enabling non-invasive, real-time cancer monitoring. Most cancer cells release high levels of EVs and cell-free DNA into circulation that carry molecular constituents of the parent tumor. Gliomas are among the most lethal of cancers and despite improved survival associated with surgery, utilizing intraoperative MR imaging guidance, as well as the postoperative use of the alkylating agent temozolomide, in combination with conformal radiation therapy and the angiogenesis inhibitor bevacizumab, glial tumors remain uniquely morbid, costly, and incurable. Brain tumor biopsy, necessary for clinical information, is itself associated with substantial morbidity and mortality. Consequently, there is a crucial need for more effective ways to determine the mutational landscape of early-stage tumors, via minimally invasive platforms, allowing for effective follow-up and biomarker-based care. The main goal of this proposal is to optimize liquid biopsy assays for the IDH1.R132H and EGFRvIII mutations in partnership with industry. This alliance includes Exosome Diagnostics, an industry leader in EV-based cancer diagnostics, offering ready capacity to develop and manufacture in-vitro diagnostic assays, and the Department of Neurosurgery at Massachusetts General Hospital, a pioneer in developing liquid biopsy signatures for brain cancer. These teams bring in their multidisciplinary expertise, innovative technologies and complementary resources to carry​ ​out​ ​the​ ​proposed​ ​work.

项目摘要 细胞外蔬菜（EV）和无细胞DNA已成为组织活检的承诺替代 实现无创，实时的癌症监测。大多数癌细胞将高水平的电动汽车和无细胞DNA释放到 携带分子的循环构成父肿瘤。神经胶质瘤是最致命的癌症和欲望 使用术中MR成像指南以及术后使用的使用，改善了与手术相关的生存率 烷基化剂替莫唑胺，结合共形辐射疗法和血管生成抑制剂 贝伐单抗，神经胶质肿瘤仍然具有独特的病态，昂贵且无法治愈。脑瘤活检，临床必要 信息本身与大量发病率和死亡率有关。因此，至关重要的需要更多 通过微创平台确定早期肿瘤的突变景观的有效方法，允许 有效的后续和基于生物标志物的护理。该提案的主要目的是优化液体活检刺激 IDH1.R132H和EGFRVIII突变与行业合作。该联盟包括外部诊断，行业 基于EV的癌症诊断的领导者，提供开发和制造体外诊断测定法的现成能力，以及 马萨诸塞州综合医院的神经外科部 脑癌。这些团队带来了他们的多学科专业知识，创新技术和完整的资源 进行拟议的工作。