Recent advances in the treatment of malignant astrocytoma

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
David A ReardonDarell D Bigner

Abstract

Malignant gliomas, including the most common subtype, glioblastoma multiforme (GBM), are among the most devastating of neoplasms. Their aggressive infiltration in the CNS typically produces progressive and profound disability--ultimately leading to death in nearly all cases. Improvement in outcome has been elusive despite decades of intensive clinical and laboratory research. Surgery and radiotherapy, the traditional cornerstones of therapy, provide palliative benefit, while the value of chemotherapy has been marginal and controversial. Limited delivery and tumor heterogeneity are two fundamental factors that have critically hindered therapeutic progress. A novel chemoradiotherapy approach, consisting of temozolomide administered concurrently during radiotherapy followed by adjuvant systemic temozolomide, has recently demonstrated a meaningful, albeit modest, improvement in overall survival for newly diagnosed GBM patients. As cell-signaling alterations linked to the development and progression of gliomas are being increasingly elucidated, targeted therapies have rapidly entered preclinical and clinical evaluation. Responses to therapies that function via DNA damage have been associated with specific mediators of resistance tha...Continue Reading

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