Glioblastoma precision therapy: From the bench to the clinic

Glioblastoma (GBM) is the most common malignancy of the central nervous system, and most patients with GBM die of the disease despite standard treatment. By clarifying the molecular abnormalities that drive the malignant phenotype of GBM, various drugs that specifically target tumor cells and the tumor microenvironment have been developed. These drugs, including drugs targeting growth factor receptors and their downstream signaling pathways, angiogenesis, aberrant metabolism, epigenetic deregulation, and aberrant immune microenvironments, have been investigated in preclinical or clinical trials. However, these drugs that significantly inhibited the growth of GBM in the preclinical stage have not produced survival benefits in patients with GBM. One reason for their failure is the lack of a definite driver gene to select patients most likely to benefit. Another reason is the inadequate pharmacokinetic properties of the drugs owing of the blood-brain barrier. In the present review, we discuss progress in the development of target therapeutic strategies. Furthermore, we discuss the development of nanomaterials that act as local drug delivery systems to penetrate the blood-brain barrier for managing GBM.