Hargrave Darren
Paediatric Oncology Unit, Royal Marsden NHS Foundation Trust, Sutton, UK.
Br J Neurosurg. 2009 Aug;23(4):351-63. doi: 10.1080/02688690903158809.
Gliomas are the most common type of paediatric brain tumour and range from benign low grade gliomas which can be resected/observed to aggressive brainstem gliomas with dismal survival rates. Current therapies rely on neurosurgery, radiotherapy, chemotherapy or combination of these conventional modalities and although histopathology helps to direct therapy, molecular pathology has so far not played a major role in the management of paediatric glioma. However, increasing knowledge of glioma biology is starting to impact on drug development towards targeted therapies. Pilocytic astrocytoma, the most common childhood low grade brain tumour, has recently been shown to harbour an activated BRAF/MAPK/ERK pathway in the majority of cases; this represents an attractive target for new agents. The molecular biology of adult malignant glioma is now well described and targeted therapies against VEGFR are already playing a role in the management of glioblastoma. It is likely that high grade gliomas in children and adults share common aberrant molecular pathways but the frequency and mechanisms involved probably will exhibit key differences and on-going comprehensive molecular analyses of paediatric high grade glioma are essential to determine which targets are important in children. However, selection for specific targeted therapy is unlikely to be based on, or restricted by, age but will require individual case by case testing for target presence in order to direct and maximise the efficacy of molecular therapy. Brainstem glioma remains a tumour with a dismal prognosis but relatively little is known about the underlying biology and progress will require a concerted effort to collect tissue by biopsy and autopsy to allow appropriate analysis to identify and validate targets. A new era of molecular based therapies offers the promise of major benefits in the management of paediatric glioma but translating this promise into reality will require further understanding of the biology driving these tumours.
神经胶质瘤是最常见的小儿脑肿瘤类型，范围从可切除/观察的良性低级别神经胶质瘤到生存率极低的侵袭性脑干神经胶质瘤。目前的治疗方法依赖于神经外科手术、放射治疗、化学疗法或这些传统治疗方式的联合使用，尽管组织病理学有助于指导治疗，但分子病理学迄今为止在小儿神经胶质瘤的管理中尚未发挥主要作用。然而，对神经胶质瘤生物学认识的不断增加开始影响靶向治疗药物的开发。毛细胞型星形细胞瘤是最常见的儿童低级别脑肿瘤，最近研究表明，在大多数病例中其具有激活的BRAF/MAPK/ERK信号通路；这是新型药物的一个有吸引力的靶点。目前对成人恶性神经胶质瘤的分子生物学已有充分描述，针对VEGFR的靶向治疗已在胶质母细胞瘤的治疗中发挥作用。儿童和成人的高级别神经胶质瘤可能具有共同的异常分子通路，但所涉及的频率和机制可能会表现出关键差异，对小儿高级别神经胶质瘤进行持续的全面分子分析对于确定哪些靶点对儿童重要至关重要。然而，选择特定的靶向治疗不太可能基于年龄或受年龄限制，而是需要对每个病例进行靶点检测，以指导和最大化分子治疗的疗效。脑干神经胶质瘤仍然是一种预后很差的肿瘤，但对其潜在生物学特性了解相对较少，要取得进展需要共同努力通过活检和尸检收集组织，以便进行适当分析以识别和验证靶点。基于分子的治疗新时代有望在小儿神经胶质瘤的管理中带来重大益处，但要将这一前景变为现实，还需要进一步了解驱动这些肿瘤的生物学特性。
