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

项目​​摘要 细胞外小泡(EVS)和游离DNA可能成为组织活检的一种有前途的替代物 实现非侵入性、实时的癌症监测。大多数癌细胞释放高水平的EVS和无细胞DNA进入 携带亲本肿瘤分子成分的循环。胶质瘤是最致命的癌症之一，尽管 利用术中磁共振成像指导以及术后应用改善与手术相关的存活率 烷化剂替莫唑胺联合适形放射治疗和血管生成抑制剂 贝伐单抗，神经胶质瘤仍然是独一无二的病态、昂贵和不可治愈的。脑肿瘤活组织检查在临床上的必要性 信息本身与相当大的发病率和死亡率有关。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记物的护理。这项建议的主要目标是优化液体活组织检查 IDH1.R132H和EGFRvIII突变与业界合作。这个联盟包括Exosome诊断公司，这是一个行业 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分析的现成能力，以及 马萨诸塞州综合医院的神经外科是开发液体活组织检查签名的先驱 脑癌。这些团队带来了他们的多学科专业知识、创新技术和互补资源，以 Carde​​Out​​The​​Proposed​​Work.

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.