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Published on: June 13, 2014
TRAIL in oncology: From recombinant TRAIL to nano- and self-targeted TRAIL-based therapies
Hassan Dianat-Moghadam1, Maryam Heidarifard2, Amir Mahari3
1Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Abstract:
TNF-related apoptosis-inducing ligand (TRAIL) selectively induces the apoptosis pathway in tumor cells leading to tumor cell death. Because TRAIL induction can kill tumor cells, cancer researchers have developed many agents to target TRAIL and some of these agents have entered clinical trials in oncology. Unfortunately, these trials have failed for many reasons, including drug resistance, off-target toxicities, short half-life, and specifically in gene therapy due to the limited uptake of TRAIL genes by cancer cells. To address these drawbacks, translational researchers have utilized drug delivery platforms. Although, these platforms can improve TRAIL-based therapies, they are unable to sufficiently translate the full potential of TRAIL-targeting to clinically viable products. Herein, we first summarize the complex biology of TRAIL signaling, including TRAILs cross-talk with other signaling pathways and immune cells. Next, we focus on known resistant mechanisms to TRAIL-based therapies. Then, we discuss how nano-formulation has the potential to enhance the therapeutic efficacy of TRAIL protein. Finally, we specify strategies with the potential to overcome the challenges that cannot be addressed via nanotechnology alone, including the alternative methods of TRAIL-expressing circulating cells, tumor-targeting bacteria, viruses, and exosomes.
Insights
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) shows promise for cancer therapy but faces challenges. Novel strategies, including nanotechnology and alternative delivery systems, aim to overcome resistance and improve TRAIL
Area of Science:
- Oncology
- Molecular Biology
- Drug Delivery Systems
Background:
- TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in tumor cells, presenting a therapeutic target in cancer.
- Clinical trials using TRAIL-targeting agents have encountered significant challenges, including drug resistance, toxicity, and poor gene uptake.
- Existing drug delivery platforms have improved TRAIL therapies but have not fully realized their clinical potential.
Purpose of the Study:
- To summarize the complex biology of TRAIL signaling and its interactions.
- To review mechanisms of resistance to TRAIL-based therapies.
- To explore strategies for enhancing TRAIL therapeutic efficacy, including nanotechnology and alternative delivery methods.
Main Methods:
- Review of TRAIL signaling pathways, including cross-talk with other signaling cascades and immune cells.
- Analysis of known resistance mechanisms against TRAIL-based cancer treatments.
- Discussion of nano-formulation approaches to improve TRAIL protein efficacy.
- Exploration of alternative delivery strategies beyond nanotechnology, such as engineered cells, bacteria, viruses, and exosomes.
Main Results:
- TRAIL biology is complex, involving intricate signaling networks and immune cell interactions.
- Multiple mechanisms contribute to resistance against TRAIL-induced apoptosis in cancer cells.
- Nanotechnology offers potential for enhancing TRAIL protein delivery and efficacy.
- Alternative delivery systems like engineered cells, bacteria, viruses, and exosomes present novel avenues to overcome TRAIL therapy limitations.
Conclusions:
- Overcoming TRAIL resistance and delivery challenges is crucial for effective cancer therapy.
- Nanotechnology shows promise in enhancing TRAIL-based treatments.
- Innovative strategies involving cellular, microbial, viral, and exosomal delivery systems are essential to fully exploit TRAIL's therapeutic potential.
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