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

项目概要 细胞外囊泡 (EV) 和无细胞 DNA 已成为组织活检的有前景的替代品，有可能 实现非侵入性实时癌症监测。大多数癌细胞释放高水平的 EV 和游离 DNA 携带母体肿瘤分子成分的循环。神经胶质瘤是最致命的癌症之一，尽管 利用术中 MR 成像指导以及术后使用 烷化剂替莫唑胺联合适形放射治疗和血管生成抑制剂 贝伐珠单抗，神经胶质瘤仍然是独特的病态、昂贵且无法治愈的。脑肿瘤活检，临床必需 信息本身与大量发病率和死亡率相关。因此，迫切需要更多 通过微创平台确定早期肿瘤突变情况的有效方法，允许 有效的随访和基于生物标志物的护理。该提案的主要目标是优化液体活检测定 与业界合作的 IDH1.R132H 和 EGFRvIII 突变。该联盟包括 Exosome Diagnostics，一个行业 基于 EV 的癌症诊断领域的领导者，提供开发和制造体外诊断测定的现成能力，以及 马萨诸塞州总医院神经外科，是开发液体活检特征的先驱 脑癌。这些团队带来了多学科专业知识、创新技术和互补资源 执行提议的工作。

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.