Growth factor biology and oncogene activation in human gliomas and their implications for specific therapeutic concepts.

Abstract

The failure of most available treatment modalities to improve the survival time and the quality of survival in patients with gliomas calls for the intense biological analysis of glial neoplasia. The untimely activation of cellular protooncogenes is often related to the process of neoplasia. Several protein growth factors as well as their cellular receptors have been identified as products of proto-oncogenes. Furthermore, these growth factors have been identified as glial mitogens in normal glial cell cultures as well as in tumors. The analysis of growth factor biology gains additional weight by the demonstration of autocrine growth factor secretion by tumor cells. The role of epidermal growth factor (EGF) and its receptor system in glial cell proliferation and differentiation is presented, with the speculation that the EGF receptor system may integrate the biological actions of many different factors, of which EGF itself may be least important. The literature on platelet-derived growth factor and insulin-like growth factors is reviewed, and the biology of fibroblast growth factor is presented in perspective with such phenomena as neovascularization and cell-matrix interactions.