NOVEL APPROACAHES FOR IMPROVING PEDIATRIC BRAFV600E GLIOMA PATIENT OUTCOMES

神经胶质瘤是影响儿童的侵袭性脑肿瘤。目前对高级别胶质瘤的治疗，通常包括手术、放疗和细胞毒性化疗，只能将受影响儿童的中位生存期延长至14个月，并导致显著的发病率。不能完全切除的低级别胶质瘤通常在化疗方法失败后用放射治疗，具有显著的神经认知和发育风险。该项目研究了一种特殊的致癌基因改变，即BRAF^^¿^发生在高达14%的小儿高级胶质瘤中。对于某些小儿胶质瘤亚型，BRAF的频率要高得多（在多形性黄色星形细胞瘤中为66%）。专门针对BRAF^(R) ^的抑制剂已经被开发出来，并对含有这种突变的黑色素瘤显示出显著的疗效。其中一种类似的抑制剂vemurafenib已经被fda批准用于黑色素瘤，并且正在研究用于治疗其他BRAF^(R)。

instnjctions):Gliomas are aggressive brain tumors that affect children. Current treatment of high-grade glioma, most ofteninvolving surgery, radiation, and cytotoxic chemotherapy, only extend median survival of affected children to14 months, and results in significant morbidity. Low-grade glioma, that cannot be completely resected aretreated with radiation, typically after failure of chemotherapy approaches, with significant resulting neuro-cognitive and developmental risks. This project addresses a specific oncogene alteration, BRAF^^¿^occurring in as many as 14% of pediatric high-grade glioma. For certain subtypes of pediatric glioma thefrequency of BRAF''^¿¿^ is much higher (66% in pleomorphic xanthoastrocytoma). Inhibitors that specificallytarget BRAF^(R)¿¿^ have been developed and have shown remarkable efficacy against melanomas that harborthis mutation. One such inhibitor, vemurafenib, has now been FDA-approved for melanoma, and is underinvestigation for treating a number of other BRAF^(R)