Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Paediatr Drugs. 2013 Feb;15(1):29-42. doi: 10.1007/s40272-012-0002-4.
Primary glial brain tumors account for the majority of primary brain tumors in children. They are classified as low-grade gliomas (LGG) or high-grade gliomas (HGG), based on specific pathologic characteristics of the tumor, resulting in disparate clinical prognoses. Surgery is a mainstay of treatment for HGG, although it is not curative, and adjuvant therapy is required. Temozolomide, an oral imidazotetrazine prodrug, while considered standard of care for adult HGG, has not shown the same degree of benefit in the treatment of pediatric HGG. There are significant biologic differences that exist between adult and pediatric HGG, and targets specifically aimed at the biology in the pediatric population are required. Novel and specific therapies currently being investigated for pediatric HGG include small molecule inhibitors of epidermal growth factor receptor, platelet-derived growth factor receptor, histone deacetylase, the RAS/AKT pathway, telomerase, integrin, insulin-like growth factor receptor, and γ-secretase. Surgery is also the mainstay for LGG. There are defined front-line, multiagent chemotherapy regimens, but there are few proven second-line chemotherapy options for refractory patients. Approaches such as the inhibition of the mammalian target of rapamycin pathway, inhibition of MEK1 and 2, as well as BRAF, are discussed. Further research is required to understand the biology of pediatric gliomas as well as the use of molecularly targeted agents, especially in patients with surgically unresectable tumors.
原发性神经胶质瘤占儿童原发性脑肿瘤的大多数。根据肿瘤的特定病理特征，它们被分为低级别神经胶质瘤 (LGG) 或高级别神经胶质瘤 (HGG)，导致不同的临床预后。手术是 HGG 的主要治疗方法，尽管它不能治愈，需要辅助治疗。替莫唑胺是一种口服咪唑并四嗪前体药物，虽然被认为是成人 HGG 的标准治疗方法，但在治疗儿童 HGG 方面并没有显示出相同程度的益处。成人和儿童 HGG 之间存在显著的生物学差异，需要针对儿科人群的特定生物学目标进行治疗。目前正在研究用于治疗儿童 HGG 的新型和特异性疗法包括表皮生长因子受体、血小板衍生生长因子受体、组蛋白去乙酰化酶、RAS/AKT 途径、端粒酶、整合素、胰岛素样生长因子受体和γ-分泌酶的小分子抑制剂。手术也是 LGG 的主要治疗方法。有明确的一线、多药化疗方案，但对于耐药患者，二线化疗选择很少。讨论了哺乳动物雷帕霉素靶蛋白途径的抑制、MEK1 和 2 以及 BRAF 的抑制等方法。需要进一步研究以了解儿科神经胶质瘤的生物学以及分子靶向药物的使用，特别是在手术不可切除的肿瘤患者中。
