New Approaches in the Treatment of Glioblastoma Multiforme

Central nervous system (CNS) malignancies are rare, but commonly fatal and glioblastoma (GBM) is the most common of the primary brain tumors. In contrast to metastatic malignancies involving the CNS, which have external blood supplies that develop when the malignant cells penetrate the blood-brain-barrier (BBB), GBM generates its own intracerebral neovascular support system. Thus, the therapeutic issues as discussed herein review the development of drugs and therapeutics that will penetrate the BBB and are cytotoxic to GBM and other brain tumors. Since GBM is a CNS malignancy with minimal effective therapeutic options available, designing drugs and therapeutics as treatment for this malignancy that penetrate, but do not disrupt the BBB is the goal of this chapter. 4-Demethylcholesteryl-4-penclomedine (DM-CHOC-PEN) was designed and developed because of its lipophilic properties that would potentiate crossing the BBB and penetrate brain tumors. The drug has now completed Phase I/II clinical trial in humans with primary brain malignancies demonstrating objective responses in GBM. In addition, preliminary experiences with naturally occurring polyphenols—curcumin, quercetin, catechins and phloretin and derivatives—are reviewed as potential naturally occurring anti-glioblastoma agents.