Enabling Drug Delivery to Cancer Cells and Tumor Endothelium: the Benefit of Targeted Therapy

Gliomas are derived from astrocytes, oligodendrocytes, and ependymal cells and account for approximately 80% of malignant primary tumors in the central nervous system (CNS). The current glioma treatment consists of surgical removal of as much of the tumor as possible, succeeded by combined radio- and chemotherapy. However, this treatment is far from sufficient due to inappropriate potency of available chemotherapeutics, leaving gliomas, especially the astrocytic tumor glioblastoma multiforme, among the most malignant conditions. A novel experimental approach is to employ targeted drug delivery specifically to the tumor. This can be done using molecular targeted drugs aiming at interfering with tumor-specific molecular signaling pathways, or targeted drug carriers that specifically bind to the cellular surface. Targetable drugs can attack signaling pathways driving cellular growth or proliferation, thus acting primarily at the cancer cells or tumor endothelial cells, respectively. Antibodies that specifically bind to cell surface molecules of glioblastoma cells or tumor endothelium are used to direct intracellular accumulation of highly toxic molecules to exert their deleterious effects. This will cause a direct demise of the glioblastoma tumor, either directly due to the targeting of cancer cell surface molecules, or indirectly due to targeting to molecules specifically expressed by newly formed endothelial cells of sprouting capillaries, leading to vascular collapse and impairment of the vascular nutritional route. This paper reviews the current progress in treatment of glioblastoma multiforme using targeted therapy to glioblastoma cells, tumor endothelial cells, and a combination of these strategies.

Keywords: Blood-brain barrier, chemotherapeutics, endothelium, glioblastoma, metabolism, targeted therapy