Scientific and Clinical Challenges within Neuro-Oncology.

Abstract

Both primary and metastatic brain tumors carry poor prognoses despite modern advances in medical therapy, radiation therapy, and surgical techniques. Gliomas, including glioblastoma (GBM), are particularly difficult to treat, and high-grade gliomas have very poor outcomes. Treatment of brain tumors involves a unique set of scientific and clinical challenges which are often not present in the treatment of systemic malignancies. With respect to scientific challenges, the anatomy and physiology of brain tumors-including the blood-brain barrier, blood-tumor barrier, and blood-cerebrospinal fluid barrier-prevent adequate drug delivery into the central nervous system (CNS). The unique nature of the immune system in the CNS as well as the immunosuppressive microenvironment of tumors such as GBM also create therapeutic roadblocks in the treatment of brain tumors. Tumor heterogeneity, particularly in GBM, has classically been thought to contribute to multitherapy resistance; however, recent data suggest that this may not be the case. Clinical challenges include brain tumor patients neurologic and medical comorbidities, as well as potential toxicity of tumor-directed treatment. Ultimately, clinical trials investigating new treatment paradigms are needed, but several roadblocks exist to good and promising clinical trial availability.