Therapeutic analysis of in vitro and in vivo brain tumor models

Abstract

Virtually all brain tumor models studied to date have demonstrated the activity of the nitrosoureas, an observation confirmed in a cohort of adult patients with high-grade gliomas. However, studies with animal brain tumor models have not led to the selection of other clinically active agents (with the possible exception of AZQ), leading investigators to conduct experiments with human CNS tumor-derived cell lines and xenografts. These studies have identified agents subsequently shown to be active in phase II clinical trials against high-grade glioma and medulloblastoma. Clinical phase III trials in progress will demonstrate if these agents result in increased disease-free survival, which is the ultimate goal of all preclinical therapeutic studies. Future research with these laboratory models may ultimately allow the definition of the mechanisms of drug resistance and the identification of modulations effective in bypassing or reversing this resistance.