Glioblastoma: Pathogenesis and Current Status of Chemotherapy and Other Novel Treatments

Abstract

Glioblastoma is one of the most common and detrimental forms of solid brain tumor, with over 10,000 new cases reported every year in the United States. Despite aggressive multimodal treatment approaches, the overall survival period is reported to be less than 15 months after diagnosis. A widely used approach for the treatment of glioblastoma is surgical removal of the tumor, followed by radiotherapy and chemotherapy. While there are several drugs available that are approved by the Food and Drug Administration (FDA), significant efforts have been made in recent years to develop new chemotherapeutic agents for the treatment of glioblastoma. This review describes the molecular targets and pathogenesis as well as the current progress in chemotherapeutic development and other novel therapies in the clinical setting for the treatment of glioblastoma.

Keywords: chemotherapy; glioblastoma; molecular targets; novel therapy; pathogenesis.

Figure 1

The IDH1/2 enzyme converts isocitrate into α-ketoglutarate (shown in the blue) while the mutant IDH1/2 enzyme converts α-ketoglutarate into 2-hydroxyglutarate (shown in orange). IDH: isocitrate dehydrogenase.

Figure 2

Reaction of acid ceramidase (ASAH1), a lysosomal enzyme that converts ceramides into sphingosine, which is further converted to sphingosine-1-phosphate (S1P) by sphingosine kinase. Ceramide promotes apoptosis while S1P stimulates cell survival and proliferation.

Figure 3

Schematic representation of a simplified overview on the PI3K/AKT/mTOR pathway with the role of phosphate and tensin homolog (PTEN) and receptor tyrosine kinase (RTK).