Recent advances in the molecular genetics of malignant gliomas disclose targets for antitumor agent perillyl alcohol

Abstract

Tumors of glial origin such as glioblastoma multiforme (GBM) comprise the majority of human brain tumors. Despite advances in surgery, radiation, and chemotherapy, the prognosis for patients with malignant glioma has not improved, emphasizing the need for a search for new chemotherapeutic drugs. Deregulated p21-Ras function, as a result of mutation, overexpression, or growth factor-induced overactivation, contributes to the growth of GBM. The monoterpene perillyl alcohol (POH) has preventive and therapeutic effects in a wide variety of preclinical tumor models and is currently under phase I and phase II clinical trials. As inhibition of posttranslational isoprenylation of Ras, a family of proteins that are involved in signal transduction is among the drug-related activities observed in this compound; POH may be a potential chemotherapeutic agent for GBM. Intranasal delivery is a practical and noninvasive approach that allows therapeutic agents that do not cross the blood-brain barrier to enter the central nervous system, reducing unwanted systemic side effects. This article describes the effect of intranasal delivery of POH in a patient with relapsed GBM.