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Recent Advances in the Treatment of Malignant Astrocytoma

From the Departments of Surgery, Pediatrics, and Pathology, Duke University Medical Center, Durham, NC

Address reprint requests to David A. Reardon, the Preston Robert Tisch Brain Tumor Center at Duke University, Duke University Medical Center, Box 3624, Durham, NC 27710; e-mail: reard003{at}mc.duke.edu

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 that may also be subject to targeted therapies. Other approaches include novel locoregional delivery techniques to overcome barriers of delivery. The simultaneous development of multiple advanced therapies based on specific tumor biology may finally offer glioma patients improved survival.

Supported by National Institutes of Health Grants No. NS20023, CA11898, and MO1 RR 30, General Clinical Research Centers Program, National Center for Research Resources, National Cancer Institute Grant No. SPORE 1 P20 CA096890, and additional funding support from the Pediatric Brain Tumor Foundation of the United States and the Accelerate Brain Cancer Cure (ABC 2) Foundation.

Authors' disclosures of potential conflicts of interest and author contributors are found at the end of this article.

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