NOVEL APPROACAHES FOR IMPROVING PEDIATRIC BRAFV600E GLIOMA PATIENT OUTCOMES

改善儿科 BRAFV600E 胶质瘤患者预后的新方法

• 批准号: 8514312
• 负责人: Charles David James
• 金额: $ 27.15万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8514312
• 关键词: Address; Affect; BRAF gene; Brain Neoplasms; Child; Childhood; Childhood Brain Neoplasm; Childhood Glioma; Cognitive; Cytotoxic Chemotherapy; Development; Diagnosis; Disease; Excision; FDA approved; Failure; Glioma; Gliomagenesis; Grant; Life; Malignant Childhood Neoplasm; Malignant Neoplasms; Morbidity - disease rate; Mutation; Neurologic; Oncogenes; Operative Surgical Procedures; Outcome; Patients; Radiation; Radiation therapy; Radiosurgery; Reproduction spores; Resected; Risk; Salvage Therapy; chemotherapy; driving force; improved; inhibitor/antagonist; melanoma; mouse model; novel; small molecule; therapeutic target; tumor

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)

神经胶质瘤是侵袭性脑肿瘤，影响儿童。目前对高级别胶质瘤的治疗，大多数通常包括手术、放疗和细胞毒化疗，仅将受累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，这会导致显著的神经认知和发育风险。该项目针对一种特定的癌基因改变，BRAF发生在多达14%的儿童高级别胶质瘤中。对于某些亚型的儿童胶质瘤，BRAF的频率要高得多（多形性黄色星形细胞瘤为66%）。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。一种这样的抑制剂vemurafenib现在已经被FDA批准用于黑色素瘤，并且正在研究用于治疗许多其他BRAF^（R）