Related Experiment Video
Updated: Jun 16, 2026
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Review: on TRAIL for malignant glioma therapy?
J M A Kuijlen1, E Bremer, J J A Mooij
1Department of Neurosurgery, University Medical Center Groningen (UMCG), University of Groningen, Groningen, The Netherlands.
Abstract:
Glioblastoma (GBM) is a devastating cancer with a median survival of around 15 months. Significant advances in treatment have not been achieved yet, even with a host of new therapeutics under investigation. Therefore, the quest for a cure for GBM remains as intense as ever. Of particular interest for GBM therapy is the selective induction of apoptosis using the pro-apoptotic tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). TRAIL signals apoptosis via its two agonistic receptors TRAIL-R1 and TRAIL-R2. TRAIL is normally present as homotrimeric transmembrane protein, but can also be processed into a soluble trimeric form (sTRAIL). Recombinant sTRAIL has strong tumouricidal activity towards GBM cells, with no or minimal toxicity towards normal human cells. Unfortunately, GBM is a very heterogeneous tumour, with multiple genetically aberrant clones within one tumour. Consequently, any single agent therapy is likely to be not effective enough. However, the anti-GBM activity of TRAIL can be synergistically enhanced by a variety of conventional and novel targeted therapies, making TRAIL an ideal candidate for combinatorial strategies. Here we will, after briefly detailing the biology of TRAIL/TRAIL receptor signalling, focus on the promises and pitfalls of recombinant TRAIL as a therapeutic agent alone and in combinatorial therapeutic approaches for GBM.
Insights
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) shows promise for glioblastoma (GBM) therapy. Recombinant TRAIL effectively kills GBM cells and can be combined with other treatments for enhanced efficacy.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Glioblastoma (GBM) remains a highly lethal brain cancer with limited treatment options.
- Significant therapeutic advances for GBM have been minimal, necessitating novel treatment strategies.
- Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in cancer cells.
Purpose of the Study:
- To review the therapeutic potential of recombinant TRAIL for GBM.
- To explore TRAIL's mechanism of action via TRAIL-R1 and TRAIL-R2.
- To evaluate TRAIL as a single agent and in combination therapies for GBM.
Main Methods:
- Review of TRAIL/TRAIL receptor signaling pathways.
- Analysis of recombinant soluble TRAIL (sTRAIL) activity against GBM cells.
- Examination of synergistic effects of TRAIL with other therapeutic agents.
Main Results:
- Recombinant sTRAIL exhibits potent anti-GBM activity with low toxicity to normal cells.
- GBM heterogeneity poses a challenge for single-agent therapies.
- TRAIL's anti-GBM effects are synergistically enhanced by various conventional and targeted therapies.
Conclusions:
- TRAIL is a promising candidate for GBM treatment due to its selective tumoricidal activity.
- Combinatorial strategies involving TRAIL offer a potential path to overcome GBM heterogeneity and improve outcomes.
- Further investigation into TRAIL-based combination therapies is warranted for GBM treatment.
