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TRAIL receptor signalling and modulation: Are we on the right TRAIL?
Devalingam Mahalingam1, Eva Szegezdi, Maccon Keane
1Department of Biochemistry and National Centre for Biomedical Engineering Science, National University of Ireland, Galway, University Road, Galway, Ireland.
Cancer Treatment Reviews
|January 2, 2009
Summary
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces cancer cell death. TRAIL receptor-targeting strategies, including variants and antibodies, show promise for overcoming resistance and improving cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) is a TNF superfamily cytokine.
- TRAIL induces apoptosis via death receptors 4 and 5 (DR4, DR5), preferentially targeting cancer cells.
- TRAIL resistance is a significant challenge in cancer therapy.
Purpose of the Study:
- To review TRAIL receptor-targeting strategies for cancer therapy.
- To discuss the apoptotic signaling pathway, prognostic implications, and combination therapies.
- To address mechanisms of TRAIL resistance and potential solutions.
Main Methods:
- Review of current literature on TRAIL and its receptors.
- Analysis of preclinical and clinical trial data.
- Discussion of molecular mechanisms of TRAIL-induced apoptosis and resistance.
Main Results:
- TRAIL selectively induces apoptosis in cancer cells.
- TRAIL resistance can be overcome by combination therapies or receptor-specific agents.
- Receptor-selective TRAIL variants and agonistic antibodies show therapeutic potential.
- Expression of TRAIL receptors has prognostic implications.
Conclusions:
- TRAIL receptor-targeting offers a promising approach for cancer treatment.
- Development of receptor-specific TRAIL variants and antibodies may enhance efficacy.
- Overcoming TRAIL resistance is crucial for successful therapeutic application.
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