Biology of Gliomas

Glioblastoma multiforme continues to be a devastating clinical problem. Despite improvements in diagnosis and supportive care. progress in the treatment of malignant gliomas is at a virtual standstill. This review covers aspects of the morphological, cell biological, biochemical, and immunological heterogeneity of human glioma cells. While acknowledging that drug delivery and kinetics (i.e., low mitotic rate, large pool of nondividing cells, and poor dead cell removal) may be important determinants of chemotherapeutic resistance, the central hypothesis advanced herein is that the major determinant of therapeutic resistance is the genotypic and phenotypic heterogeneity of glioma cells. The detailed karyotypic. phenotypic. cell biological, and chemotherapeutic response heterogeneity of permanent cell lines derived from human gliomas is reviewed. A literature review of glioma heterogeneity with regard to karyotype, cytophotometric and flow cytometric determination of DNA, and chemotherapeutic response of permanent cell line-derived and glioma biopsyderived tumors in athymic mice was made. There is abundant evidence that permanent glioma cell lines differ significantly in karyotype, morphology, growth properties, and chemotherapeutic response. There is another large body of evidence implicating morphological, genotypic, and phenotypic heterogeneity within gliomas at the time of surgical removal. The challenge of the next decade of glioma research will be to demonstrate the biological and clinical significance or the lack thereof of the cellular heterogeneity of gliomas. Recognizing the limits of glioma heterogeneity may allow the design of a successful multimodality therapy for this class of tumors, which has remained so recalcitrant to treatment by surgery, radiation, chemotherapy, and immunotherapy. (Neurosurgery 9:320-326, 1981)