The biology of malignant gliomas--a comprehensive survey

Malignant gliomas constitute a morphologically diverse group of neoplasms that respond poorly to therapy. The median survival of patients with glioblastoma multiforme, the most common malignant glioma, is only 11 months. Several factors influence the therapeutic resistance of malignant gliomas, including tumor heterogeneity, local invasion, and non-uniform vascular permeability to therapeutic agents. Malignant gliomas vary in their expression of specific marker proteins such as glial fibrillary acidic protein and fibronectin, in their expression of specific cell surface antigens, in their in vitro growth properties and tumorigenicity in athymic nude mice, and in their chromosomal composition and DNA content. This biochemical, immunochemical, biologic, and chromosomal heterogeneity is observed between different gliomas and within individual gliomas both in vivo and in vitro. Marked vascular hyperplasia, a characteristic feature of malignant gliomas, is induced by growth factors that may stimulate not only vascular cells but also glioma cells. There is also heterogeneity in the ultrastructure and the permeability of glioma blood vessels. In animal brain tumor models, vascular permeability varies not only between different models but between different tumors and between different areas of a single tumor. An understanding of the cell biology of malignant gliomas may identify the factors that determine therapeutic resistance and provide strategies to overcome these factors.