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Pyroptosis in cancer therapy: a double-edged sword for immune activation and tumor progression
Ali Alishvandi1,2, Cena Aram3, Farzaneh Faraji Shahrivar4
1Student Research Committee, Iranshahr University of Medical Sciences, Iranshahr, Iran.
Abstract:
Pyroptosis, a caspase-dependent form of inflammatory programmed cell death, is driven by inflammasome activation and gasdermin-mediated membrane pore formation. Its immunogenic nature has attracted increasing attention in oncology, particularly for overcoming therapeutic challenges such as chemoresistance, radiotherapy failure, and immune checkpoint blockade non-responsiveness. By promoting the release of pro-inflammatory cytokines and damage-associated molecular patterns (DAMPs), pyroptosis can enhance antitumor immunity and reshape the tumor microenvironment (TME). However, sustained or dysregulated pyroptosis can lead to chronic inflammation, radiotherapy-induced tissue injury, and tumorigenesis, making it a double-edged sword. Emerging evidence shows that pyroptosis exhibits cancer-type-specific roles, depending on the molecular context and the extent of activation. Therefore, understanding the molecular regulators, tumor-specific signaling, and temporal dynamics of pyroptosis is essential for its therapeutic modulation. This review comprehensively outlines the dual roles of pyroptosis in cancer progression and treatment, discusses its molecular mechanisms, and highlights recent strategies to harness or suppress pyroptosis for therapeutic gain. Targeting pyroptosis offers a promising, yet complex, avenue for immune-enhancing cancer therapies.
Insights
Pyroptosis, an inflammatory cell death process, shows dual roles in cancer. Understanding its mechanisms is key to developing new immune-enhancing cancer therapies.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Pyroptosis is a programmed inflammatory cell death pathway.
- It involves inflammasome activation and gasdermin pore formation.
- Pyroptosis has potential in overcoming cancer treatment resistance.
Purpose of the Study:
- To review the dual roles of pyroptosis in cancer progression and treatment.
- To discuss pyroptosis molecular mechanisms.
- To highlight strategies for therapeutic modulation of pyroptosis.
Main Methods:
- Comprehensive literature review.
- Analysis of molecular mechanisms.
- Discussion of emerging therapeutic strategies.
Main Results:
- Pyroptosis can enhance antitumor immunity by releasing cytokines and DAMPs.
- Dysregulated pyroptosis may promote inflammation and tumorigenesis.
- Pyroptosis exhibits cancer-type-specific roles.
Conclusions:
- Targeting pyroptosis offers a promising strategy for cancer therapy.
- Modulating pyroptosis requires understanding its complex roles and molecular regulators.
- Pyroptosis presents a complex avenue for immune-enhancing cancer treatments.
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