NOVEL APPROACAHES FOR IMPROVING PEDIATRIC BRAFV600E GLIOMA PATIENT OUTCOMES

例：胶质瘤是侵袭性的脑瘤，影响儿童。目前对高级别胶质瘤的治疗，大多涉及手术、放疗和细胞毒性化疗，仅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失败后接受放射治疗，导致显著的神经认知和发育风险。该项目针对的是一种特殊的癌基因改变，在多达14%的儿童高级别胶质瘤中发生。在某些亚型的儿童胶质瘤中，BRAF‘’的频率要高得多(在多形性黄色星形细胞瘤中占66%)。专门针对BRAF^(R)的抑制剂已经开发出来，并对抑制这种突变的黑色素瘤显示出显著的疗效。一种这样的抑制剂，vemurafenib，现在已经被FDA批准用于黑色素瘤，并正在接受治疗其他一些BRAF^(R)的研究。

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)