TRAIL combinations: The new 'trail' for cancer therapy (Review)
Alaa Refaat1, Ahmed Abd-Rabou1, Asmaa Reda1
1Center for Aging and Associated Diseases, Zewail City of Science and Technology, Giza 12588, Egypt.
Abstract:
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) therapy is anticipated to be one of the most effective cancer treatments. However, resistance to TRAIL therapy remains a challenge facing the development of anticancer strategies. To circumvent this problem, TRAIL combinations have been experimented with for over ten years to induce synergism or sensitize resistant cancer cells. By analyzing the signaling pathways triggered by these combinations, this review has defined a set of core targets for novel combinatorial treatments. The review suggests specific pathways to be targeted together with TRAIL for more efficient treatment, including cellular FLICE inhibitory protein and its downstream survival factors, the Bcl-2 family and other prominent targets. The suggested pathways provide new avenues for more effective TRAIL-based cancer therapy.
Insights
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) therapy shows promise for cancer treatment. Combining TRAIL with specific targeted pathways can overcome resistance and improve therapeutic efficacy in cancer cells.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) therapy is a promising anticancer strategy.
- Cancer cells often develop resistance to TRAIL therapy, limiting its clinical effectiveness.
- Combinatorial approaches using TRAIL are being explored to overcome this resistance.
Purpose of the Study:
- To review and define core targets for novel TRAIL-based combinatorial cancer treatments.
- To identify signaling pathways that can synergize with TRAIL to sensitize resistant cancer cells.
- To provide a basis for developing more effective TRAIL-combined cancer therapies.
Main Methods:
- Systematic review of studies investigating TRAIL combinations.
- Analysis of signaling pathways activated by TRAIL in combination therapies.
- Identification of key molecular targets for synergistic or sensitizing effects.
Main Results:
- TRAIL resistance is a significant hurdle in cancer treatment development.
- Analysis identified cellular FLICE inhibitory protein (c-FLIP) and Bcl-2 family proteins as key targets.
- Specific pathway combinations can overcome TRAIL resistance and enhance cancer cell death.
Conclusions:
- Targeting specific pathways alongside TRAIL offers a promising strategy to enhance cancer therapy.
- c-FLIP and Bcl-2 family proteins are critical targets for overcoming TRAIL resistance.
- Novel combinatorial treatments hold potential for more effective TRAIL-based cancer treatment.
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