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Published on: October 27, 2014
Overcoming TRAIL Resistance for Glioblastoma Treatment
Longfei Deng1, Xuan Zhai2, Ping Liang2
1Cancer Center, Medical Research Institute, Southwest University, Chongqing 400716, China.
Abstract:
The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) shows a promising therapeutic potential in cancer treatment as it exclusively causes apoptosis in a broad spectrum of cancer cells through triggering the extrinsic apoptosis pathway via binding to cognate death receptors, with negligible toxicity in normal cells. However, most cancers, including glioblastoma multiforme (GBM), display TRAIL resistance, hindering its application in clinical practice. Recent studies have unraveled novel mechanisms in regulating TRAIL-induced apoptosis in GBM and sought effective combinatorial modalities to sensitize GBM to TRAIL treatment, establishing pre-clinical foundations and the reasonable expectation that the TRAIL/TRAIL death receptor axis could be harnessed to treat GBM. In this review, we will revisit the status quo of the mechanisms of TRAIL resistance and emerging strategies for sensitizing GBM to TRAIL-induced apoptosis and also discuss opportunities of TRAIL-based combinatorial therapies in future clinical use for GBM treatment.
Insights
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) shows promise for cancer therapy by inducing apoptosis in cancer cells. This review explores overcoming TRAIL resistance in glioblastoma multiforme (GBM) for effective treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells via the extrinsic pathway.
- TRAIL exhibits negligible toxicity in normal cells, highlighting its therapeutic potential.
- Glioblastoma multiforme (GBM) often displays resistance to TRAIL, limiting its clinical application.
Purpose of the Study:
- To review mechanisms of TRAIL resistance in GBM.
- To explore novel strategies for sensitizing GBM to TRAIL-induced apoptosis.
- To discuss TRAIL-based combinatorial therapies for GBM treatment.
Main Methods:
- Literature review of studies on TRAIL resistance mechanisms in GBM.
- Analysis of emerging strategies to enhance TRAIL sensitivity.
- Discussion of preclinical findings and future clinical prospects.
Main Results:
- TRAIL resistance is a significant challenge in GBM treatment.
- Novel mechanisms regulating TRAIL-induced apoptosis in GBM have been identified.
- Combinatorial approaches show promise in sensitizing GBM to TRAIL.
Conclusions:
- Harnessing the TRAIL/TRAIL death receptor axis is a viable strategy for GBM treatment.
- Understanding TRAIL resistance mechanisms is crucial for developing effective therapies.
- TRAIL-based combinatorial therapies hold potential for future clinical use in GBM.
