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TRIAL-based combination therapies in cancers
Qiumin Deng1, Luxuan Chen1, Gui Zhang1
1MOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
Abstract:
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) shows promising therapeutic potential in cancer treatment as it is able to trigger extrinsic apoptotic pathways by binding to the cognate death receptor, causing broad-spectrum apoptosis in cancer cells with negligible toxicity to normal cells. However, the majority of cancers display resistance to TRAIL, limiting its clinical utility. Overcoming resistance to TRAIL therapies remains a challenge in the development of effective anti-cancer strategies. To address the limitations of TRAIL therapy, a viable alternative approach involves combining TRAIL with more potent drugs compared to monotherapy. This combination strategy aims to induce synergistic effects or sensitize drug-resistant cancer cells. This review provides an overview of relevant modalities of TRAIL combination therapy, highlighting different drug classes. The findings demonstrate that combining TRAIL with other agents can effectively counteract resistance observed with TRAIL therapies in cancer. These findings lay a foundation for future advancements in TRAIL-based therapies for treating various cancers.
Insights
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) shows promise for cancer treatment. Combining TRAIL with other drugs effectively overcomes cancer cell resistance, enhancing therapeutic outcomes.
Area of Science:
- Molecular Biology
- Cancer Therapeutics
- Apoptosis Signaling
Background:
- Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells via extrinsic pathways.
- Cancer cells frequently develop resistance to TRAIL monotherapy, limiting its clinical application.
- Overcoming TRAIL resistance is crucial for developing effective anti-cancer strategies.
Purpose of the Study:
- To review combination therapy approaches for overcoming TRAIL resistance in cancer.
- To highlight various drug classes used in conjunction with TRAIL.
- To provide a foundation for advancing TRAIL-based cancer treatments.
Main Methods:
- Literature review of TRAIL combination therapies.
- Analysis of different drug classes combined with TRAIL.
- Evaluation of synergistic effects and sensitization of resistant cancer cells.
Main Results:
- Combination strategies effectively counteract TRAIL resistance in various cancers.
- Synergistic effects observed when TRAIL is combined with other potent agents.
- Sensitization of drug-resistant cancer cells is a key outcome.
Conclusions:
- Combining TRAIL with other drugs is a viable strategy to overcome cancer resistance.
- This approach enhances the therapeutic potential of TRAIL in cancer treatment.
- Findings support future development of advanced TRAIL-based combination therapies.
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