Gasdermin E (GSDME)
Gasdermin E (GSDME), also known as DFNA5, is a pore-forming protein in the gasdermin family that is best known for its role in regulated cell death.
Gasdermin E (GSDME), also known as DFNA5, is a pore-forming protein in the gasdermin family that is best known for its role in regulated cell death. In many biological contexts, GSDME is cleaved by caspase-3 (caspase-3), releasing an N-terminal fragment that can disrupt the plasma membrane and drive pyroptosis, a lytic and highly inflammatory form of cell death. This places GSDME at the intersection of apoptosis and pyroptosis, where it can convert a caspase-3–mediated apoptotic signal into membrane rupture, cytokine release, and immunogenic cell death.
Because of this switch-like function, GSDME has attracted substantial interest in cancer biology and therapeutic development. In tumor settings, activation of the caspase-3/GSDME axis has been explored as a way to overcome apoptosis resistance and promote antitumor immunity. Recent studies have linked GSDME-dependent pyroptosis with enhanced release of proinflammatory cytokines, increased antigen presentation, and improved immune-cell recruitment, including CD8+ T cells, often in combination with checkpoint inhibitor strategies such as anti-PD-1/PD-L1 or anti-CTLA-4 therapy.
Where the papers sit
10 papers from the last 6 months study Gasdermin E (GSDME) directly · updated from PubMed 12 Oct 2026
Study type 0 clinical trials · 10 preclinical
Themes 3 themes · 1 new direction
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Cell Death Pathway Targeting
GSDME-associated pyroptosis is being linked to apoptosis, mitotic damage, and inflammatory signaling as a way to overcome treatment-resistant disease. TLR4-JNK-Caspase-3 signaling, XIAP-coordinated PKC activity, and dual TRIP13-Aurora A inhibition represent distinct entry points. Hypoxia and HIF-1α connect related cell-death pathways to inflammation and fibrosis in thyroid eye disease. The field is moving toward mechanism-defined combinations rather than a single universal trigger.
4 papers · 40%
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GSDME Pyroptosis Biology
GSDME-mediated pyroptosis is being used to reshape tumor immunity and improve radiation responses. Biomimetic vesicles and exosome-liposome platforms aim to expose tumor antigens, counter immune evasion, and activate antitumor responses in glioblastoma and other tumors. Astrocytic GSDME in sepsis-associated cognitive dysfunction extends the mechanism beyond cancer. The shared biology is clear, but therapeutic direction remains disease-specific.
3 papers · 30%
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Photopyroptosis for Cancer Immunity
Nanomaterial-triggered pyroptosis is moving toward cancer immunotherapy that couples reactive oxygen species with mitochondrial injury. Mitochondrial DNA release, dendritic-cell activation, and innate immune signaling recur across the platforms. Near-infrared photoactivation and alkaline-phosphatase-responsive probes seek spatially controlled tumor killing. Combining these approaches with anti-PD-1 therapy is the main therapeutic aim.
3 papers · 30%
GSDME is a pathogenic mediator of sepsis-associated cognitive dysfunction, not only a therapeutic trigger of tumor-cell pyroptosis
The cecal-ligation-and-puncture model of sepsis-associated encephalopathy found that GSDME expression and cleavage in hippocampal astrocytes contributed to cognitive impairment, while astrocyte-specific GSDME knockdown and geniposide-mediated inhibition improved cognition 42055495Apr. This places GSDME in a disease-promoting astrocyte process and identifies its inhibition, rather than its induction to kill cancer cells, as the therapeutic direction.
Papers
The 10 papers from the last 6 months that study Gasdermin E (GSDME) directly, newest first, by theme and by study type. Study types come from PubMed publication types and MeSH headings.
By theme
Cell Death Pathway Targeting (4)
- Digoxin inhibits HIF-1α to attenuate inflammation and fibrosis in thyroid eye disease. Biochemical and biophysical research communications · 24 Jul 2026 PMID 42497831
- Targeting XIAP-coordinated PKC signaling resensitizes PD-1-refractory tumors for rechallenge. Proceedings of the National Academy of Sciences of the United States of America · 3 Jun 2026 PMID 42234523
- Cauloside A interacts with TLR4 to induce JNK/Caspase-3/GSDME-dependent pyroptosis in non-small cell lung cancer cells. International immunopharmacology · 5 May 2026 PMID 42085840
- Dual Inhibition of TRIP13 and Aurora A Induces Mitotic DNA Damage and Concurrent Pyroptotic-Apoptotic Cell Death in Rb-Deficient Cancer Cells. Clinical cancer research : an official journal of the American Association for Cancer Research · 21 Apr 2026 PMID 42013305
GSDME Pyroptosis Biology (3)
- Biomimetic nanovesicle mediated GSDME delivery reprograms the tumor immune microenvironment via pyroptosis to enhance radiotherapy. Journal of controlled release : official journal of the Controlled Release Society · 23 Jul 2026 PMID 42492635
- A Screening-Guided Biomimetic Exosome-Liposome Hybrid Nanoplatform Enables Pyroptosis-Enhanced Immune Reprogramming in Glioblastoma. ACS nano · 17 Jul 2026 PMID 42466899
- The role of astrocytic GSDME in Sepsis-associated cognitive dysfunction. International immunopharmacology · 29 Apr 2026 PMID 42055495
Photopyroptosis for Cancer Immunity (3)
- Manganese Vacancy-Engineered Prussian Blue Triggers Pyroptosis-Driven Innate Immunity for Second Near-Infrared Region Photoimmunotherapy. ACS nano · 7 Jun 2026 PMID 42251536
- In Situ Activating a Protein-Complexed Quenched Probe via Alkaline Phosphatase Response for Pyroptosis-Mediated Cancer Immunotherapy. Angewandte Chemie (International ed. in English) · 4 Jun 2026 PMID 42241249
- Mitochondria-Targeted Zwitterionic Nanogels Trigger Photopyroptosis for Enhanced Cancer Therapy. Small (Weinheim an der Bergstrasse, Germany) · 17 May 2026 PMID 42143709
By study type
Preclinical: animal, cell and lab studies (10)
- Digoxin inhibits HIF-1α to attenuate inflammation and fibrosis in thyroid eye disease. Biochemical and biophysical research communications · 24 Jul 2026 PMID 42497831
- Biomimetic nanovesicle mediated GSDME delivery reprograms the tumor immune microenvironment via pyroptosis to enhance radiotherapy. Journal of controlled release : official journal of the Controlled Release Society · 23 Jul 2026 PMID 42492635
- A Screening-Guided Biomimetic Exosome-Liposome Hybrid Nanoplatform Enables Pyroptosis-Enhanced Immune Reprogramming in Glioblastoma. ACS nano · 17 Jul 2026 PMID 42466899
- Manganese Vacancy-Engineered Prussian Blue Triggers Pyroptosis-Driven Innate Immunity for Second Near-Infrared Region Photoimmunotherapy. ACS nano · 7 Jun 2026 PMID 42251536
- In Situ Activating a Protein-Complexed Quenched Probe via Alkaline Phosphatase Response for Pyroptosis-Mediated Cancer Immunotherapy. Angewandte Chemie (International ed. in English) · 4 Jun 2026 PMID 42241249
- Targeting XIAP-coordinated PKC signaling resensitizes PD-1-refractory tumors for rechallenge. Proceedings of the National Academy of Sciences of the United States of America · 3 Jun 2026 PMID 42234523
- Mitochondria-Targeted Zwitterionic Nanogels Trigger Photopyroptosis for Enhanced Cancer Therapy. Small (Weinheim an der Bergstrasse, Germany) · 17 May 2026 PMID 42143709
- Cauloside A interacts with TLR4 to induce JNK/Caspase-3/GSDME-dependent pyroptosis in non-small cell lung cancer cells. International immunopharmacology · 5 May 2026 PMID 42085840
- The role of astrocytic GSDME in Sepsis-associated cognitive dysfunction. International immunopharmacology · 29 Apr 2026 PMID 42055495
- Dual Inhibition of TRIP13 and Aurora A Induces Mitotic DNA Damage and Concurrent Pyroptotic-Apoptotic Cell Death in Rb-Deficient Cancer Cells. Clinical cancer research : an official journal of the American Association for Cancer Research · 21 Apr 2026 PMID 42013305
Written from 10 PubMed abstracts, each one listed by PMID above. Published: 2026-06-15. Last written: 2026-08-27 by GPT. Drafted by language models from published abstracts; not medical advice.