Current approaches in enhancing TRAIL therapies in glioblastoma

Glioblastoma (GBM) is the most prevalent, aggressive, primary brain cancer in adults and continues to pose major medical challenges due in part to its high rate of recurrence. Extensive research is underway to discover new therapies that target GBM cells and prevent the inevitable recurrence in patients. The pro-apoptotic protein tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has attracted attention as an ideal anticancer agent due to its ability to selectively kill cancer cells with minimal toxicity in normal cells. Although initial clinical evaluations of TRAIL therapies in several cancers were promising, later stages of clinical trial results indicated that TRAIL and TRAIL-based therapies failed to demonstrate robust efficacies due to poor pharmacokinetics, resulting in insufficient concentrations of TRAIL at the therapeutic site. However, recent studies have developed novel ways to prolong TRAIL bioavailability at the tumor site and efficiently deliver TRAIL and TRAIL-based therapies using cellular and nanoparticle vehicles as drug loading cargos. Additionally, novel techniques have been developed to address monotherapy resistance, including modulating biomarkers associated with TRAIL resistance in GBM cells. This review highlights the promising work to overcome the challenges of TRAIL-based therapies with the aim to facilitate improved TRAIL efficacy against GBM.