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  • Title: Paediatric high and low grade glioma: the impact of tumour biology on current and future therapy.
    Author: Hargrave D.
    Journal: Br J Neurosurg; 2009 Aug; 23(4):351-63. PubMed ID: 19637006.
    Abstract:
    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.
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