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The Clinical Application of Tumor Treating Fields Therapy in Glioblastoma
Published on: April 16, 2019
Current approaches in enhancing TRAIL therapies in glioblastoma
Morrent Thang1,2, Clara Mellows2, Alison Mercer-Smith2
1Neuroscience Center, University of North Carolina-Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.
Abstract:
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.
Insights
Glioblastoma (GBM) treatments face challenges due to cancer recurrence. Novel strategies are improving tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) delivery and overcoming resistance for better GBM therapy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Glioblastoma (GBM) is an aggressive primary brain cancer with high recurrence rates, necessitating novel therapeutic approaches.
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) shows promise as a cancer-selective agent but faces pharmacokinetic limitations.
Purpose of the Study:
- To review recent advancements in overcoming challenges associated with TRAIL-based therapies for glioblastoma.
- To highlight strategies for enhancing TRAIL bioavailability and efficacy in GBM treatment.
Main Methods:
- Review of current literature on TRAIL therapy, drug delivery systems, and resistance mechanisms in GBM.
- Analysis of novel approaches utilizing cellular and nanoparticle vehicles for TRAIL delivery.
- Examination of methods to modulate TRAIL resistance biomarkers in GBM cells.
Main Results:
- Development of advanced drug delivery systems (cellular and nanoparticle vehicles) to improve TRAIL bioavailability at the tumor site.
- Emerging techniques to address and overcome intrinsic or acquired resistance to TRAIL monotherapy in GBM.
- Identification of key biomarkers and strategies for modulating TRAIL resistance.
Conclusions:
- Overcoming pharmacokinetic limitations and TRAIL resistance are critical for successful GBM therapy.
- Novel delivery systems and resistance modulation strategies show significant promise for enhancing TRAIL efficacy against glioblastoma.
- Further research into these advanced TRAIL-based therapies could lead to improved clinical outcomes for GBM patients.
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