Neurosurg Focus
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Despite recent advances in operative techniques, chemotherapy, and radiotherapy, the prognosis in patients with glioblastoma multiforme (GBM) remains poor; the majority die within a year of diagnosis. Although often effective at reducing mass effect and tumor burden, surgical debulking and cytotoxic therapies have never demonstrated an unequivocally significant benefit in treating patients with GBM. This shortcoming has led to the development of molecules that target specific steps in the transduction pathways of high-grade glioma cells. In this article the authors review various cellular and extracellular signaling pathways that may prove promising in the treatment of patients with malignant glioma.
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Established treatments such as surgery, radiation, and chemotherapy have only minimally altered the median survival time of patients with glioblastoma multiforme, the most common malignant brain tumor. These failures reflect the highly invasive nature of the disease, as well as the fact that few cells are actively dividing at any given time. ⋯ Over the past decade, laboratory studies and early clinical trials have raised the hope that these therapeutic requirements may be fulfilled by gene therapy in which nonreplicating transgene-bearing viruses, oncolytic viruses, or migratory stem cells are used to deliver tumoricidal transgenes. The authors review the principles behind these approaches and their initial results.
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Glioblastomas multiforme (GBMs) are highly vascular brain tumors characterized by abnormal vessel structures in vivo. This finding supports the theory that glioma-associated endothelial cells (ECs) have intrinsically different properties from ECs in normal human brain. Therefore, identification of the functional and phenotypic characteristics of tumor-associated ECs is essential for designing a rational antiangiogenic therapy. ⋯ The GBM-associated ECs are resistant to cytotoxic drugs, and they undergo less apoptosis than control cells. Also, GBM-associated ECs migrate faster than controls and constitutively produce high levels of growth factors such as endothelin-1, interleukin-8, and vascular endothelial growth factor. An understanding of these unique characteristics of glioma-associated ECs is important for the development of novel antiangiogenic agents that specifically target tumor-associated ECs in gliomas.
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Review
Standard treatment and experimental targeted drug therapy for recurrent glioblastoma multiforme.
Glioblastoma multiforme (GBM) tumors almost invariably recur despite initial treatments. Correct diagnosis using a variety of imaging techniques and the involvement of a multidisciplinary tumor board are critical for evaluating each stage of a patient's progression and determining optimal management. Standard therapies for recurrence generally include repeated resection, radiation therapy, chemotherapy, and supportive care; however, salvage therapy must be highly individualized, and not all patients are eligible for every type of standard therapy. ⋯ Experimental targeted drug therapies have been developed to inhibit aberrant cell-signaling pathways involved in tumorigenesis, and enrolling patients in clinical trials using these therapies is another option for treatment of recurrent GBM. The use of these novel therapies is often confined to large research institutions, but the severe limitations of standard treatment options make it important to highlight the potential of experimental therapies. In this paper the authors outline standard therapies and review the emerging role of targeted drug therapy in the treatment of recurrent GBM.
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Adenoviruses historically have been one of the main vectors used in human gene therapy. To date, the majority of brain tumor trials of these vectors have used replication-defective viruses. ⋯ These adenoviruses, once they are rendered conditionally replicative by transductional and transcriptional modifications, offer significant promise for patients with malignant glioma. In this review, the authors discuss the genetic approaches to adenoviral modification and their applications in the field of neurooncology.