Molecular Neuro-oncology and the Challenge of the Blood-Brain Barrier

Despite epochal advances in brain imaging, radiation delivery, and neurosurgical sophistication, the survival of patients with primary malignant astrocytomas has not been met with commensurate progress. While temozolomide, an alkylating agent, has demonstrated a survival benefit, median survival in the past decade of patients with glioblastoma (GBM) remains an obdurate 15 months and add-on therapies have not significantly prolonged life. It is likely that further advances may need to await additional discoveries that are slowly being revealed by molecular exploration of the tumor genome. This review summarizes many recent developments in molecular neuro-oncology and examines formidable challenges imposed by the highly restrictive properties of the blood-brain barrier (BBB) that impact effective drug delivery.