Background
The characteristics of pyroptosis distinguished from other forms of cell death
Type of cell death | Morphological characteristics | Inducers | Initiator caspase | Major executor |
---|---|---|---|---|
Apoptosis | Bubbling plasma membrane, shrunkern cells, chromatin aggreegation and condensation | Fas, TNFR, TRAIL-R. TLRs, DNA damage, hypoxia | Caspase-8/10/3/9/6/7 | Caspases |
Necroptosis | Disrupted plasma membrane integrity, cell contents leakage | TNFR1, Fas, LPS, TLR3/4 | Caspase-8/10 | RIPK1, RIPK3, MLKL |
Ferroptosis | Shrunken mitochondria, increased membrane density and decreased mitochondrial cristae | Fe3 + , cystine, lipid peroxidation, | No | GPX4 |
Pyroptosis | Cell swelling, pore formation on cell embranes, bubbling and disrupted plasma membrane | DAMPs, PAMPs, acterial infections, LPS, chemotherapy drugs, TNF, GZMA, GZMB | Caspase-1/4/5/11/8 | Gasdermins |
Cuproptosis | Shrunken mitochondria, disrupted plasma membrane, damage to the endoplasmic reticulum | Cu2 + | No | FDX1 |
Molecular mechanisms of pyroptosis
The canonical pathway
The non-canonical pathway
Alternative pathways
Gasdermin family members in cancer progression
The role of GSDMA in cancer progression
Human gasdermin | Mouse gasdermin | Activated by | Tissue expression | Related cancers |
---|---|---|---|---|
GSDMA | Gsdma1, Gsdma2, Gsdma3 | streptococcal pyrogenic exotoxin B | Skin, gastrointestinal tract | Gastric cancer, ovarian cancer |
GSDMB | N | GZMA, GZMB, caspase3/6/7 | Normal tissues and tumor cells | Gastric cancer, cervical cancer, hepatocarcinoma, bladder cancer, clear cell renal cell carcinoma, bladder cancer |
GSDMC | Gsdmc1, Gsdmc2, Gsdmc3, Gsdmc4 | Caspase8 | Melanoma cells | Melanoma, lung adenocarcinoma, breast cancer, gastric cancer, colorectal cancer, kidney clear cell cancer |
GSDMD | Gsdmd | Caspase1/4/5/8/11, neutrophil elastase, cathepsin G | Nucleus, plasma membrane | Hepatocellular carcinoma, non-small lung cancer, gastric cancer, |
GSDME | Gsdme | Caspase3 | Plasma membrane, mitochondrial | Breast cancer, lung adenocarcinoma, oesophageal squamous cell carcinoma, oral squamous cell carcinoma, colorectal cancer, |
The role of GSDMB in cancer progression
The role of GSDMC in cancer progression
The role of GSDMD in cancer progression
The role of GSDME in cancer progression
The immune-modulatory effects of pyroptosis
Pyroptosis-related cytokine IL-1β
Pyroptosis-related cytokine IL-18
Pyroptosis-related cytokine HMGB1
Pyroptosis effects on immune cells
Potential strategies targeting pyroptosis
Targets | Agents | Mechanism | Tumor cells type | References |
---|---|---|---|---|
GSDMA3 | A bioorthogonal chemical system | The Phe-BF3 selectively cleaved GSDMA3 | Hela cell, EMT6, 4T1 | [133] |
GSDMB | Nanocapsule loaded with an anti-GSDMB antibody | Inhibition the expression of GSDMB | Breast cancer | [183] |
GSDMC | Listeria | Increase GSDMC expression, recruit immune cells | Colorectal cancer | [185] |
Daunorubicin, epirubicin, actinomycin-D | Increase GSDMC expression, | Breast cancer | [53] | |
GSDMD | Cisplatin | Activate caspase-1/GSDMD pathway, increase MEG3 expression | Breast cancer | [187] |
Cucurbitacin B | Bind to TLR4 and increase ROS inductiona and cytosolic calcium release | Non-small cell lung cancer | [191] | |
ZrNPs | Induce GSDMD cleavage, activate caspase-1 | Breast cancer | [192] | |
CXCR4-targeted nanotoxin | Interact with CXCR4 receptor | Colorectal cancer | [193] | |
Dimethyl fumarate | Inhibit GSDMD | Hepatocellular carcinoma | [116] | |
GSDME | Decitabine | Upregulate GSDME expression and switch apoptosis to pyroptosis | Breast cancer | [24] |
Triptolide | Activate caspase-3 | Head and neck cancer | [33] | |
Lobaplatin | Activate caspase-3 | Colon cancer | ||
Cisplatin | Activate caspase-3 | Non-small cell lung cancer | [199] | |
Carrier-free nanoplatform assembled with cytarabine and chlorin e6 | Accumulate ROS and induce immunogenic cell death, release HMGB1, ATP and calcitonin, activate GSDME | Breast cancer | [200] | |
BNP | Activate caspase-3, promote cytochrome c release, increase GSDME expression | Breast cancer | [203] | |
CXCR4-targeted nanotoxins | Activate caspase-3 | Head and neck cancer | [204] | |
Nanoruner platform | Activate phospholipase C signalling transduction in early endosomes | [209] | ||
Metformin | Activate AMPK/SIRT1 signaling, promote NF-κB expression | Hepatoblastoma, colon cancer, breast cancer |
Targets | Drugs | Phase | Conditions | Sponsor | Gov identifier |
---|---|---|---|---|---|
IL-1β | Canakinumab | 3 | Non-Small-Cell Lung | Novartis Pharmaceuticals | NCT03626545 |
IL-1β | Canakinumab | 3 | Non-Small-Cell Lung | Novartis Pharmaceuticals | NCT03631199 |
IL-1β | Canakinumab | 2 | Chronic Myelomonocytic Leukemia | M.D. Anderson Cancer Center | NCT04239157 |
IL-1β | Canakinumab | Myelodysplastic Syndrome | |||
IL-1β | Canakinumab | Recurrent Chronic Myelomonocytic Leukemia | |||
IL-1β | Canakinumab | Recurrent Myelodysplastic Syndrome | |||
IL-1β | Canakinumab | Refractory Chronic Myelomonocytic Leukemia | |||
IL-1β | Canakinumab | Refractory Myelodysplastic Syndrome | |||
IL-1β | Canakinumab | 1 | Metastatic Pancreatic Ductal Adenocarcinoma | Pancreatic Cancer Action Network | NCT04581343 |
IL-1β | Canakinumab | 3 | Lung Cancer | Mario Negri Institute for Pharmacological Research | NCT05725343 |
IL-1β | Canakinumab | 2 | Non-small Cell Lung Cancer | Memorial Sloan Kettering Cancer Center | NCT04905316 |
IL-1β | Canakinumab | 3 | Non-small Cell Lung Cancer | Novartis Pharmaceuticals | NCT03447769 |
IL-1β | Canakinumab | 2 | Non-small Cell Lung Cancer | Novartis Pharmaceuticals | NCT03968419 |
IL-1β | Canakinumab | 2 | Lung Carcinoma | M.D. Anderson Cancer Center | NCT04789681 |
IL-1β | Canakinumab | 1 | Triple Negative Breast Cancer | Novartis Pharmaceuticals | NCT03742349 |
IL-1β | Canakinumab | 3 | Metastatic Pancreatic Cancer | Pancreatic Cancer Action Network | NCT04229004 |
IL-1β | Canakinumab | Metastatic Pancreatic Adenocarcinoma | |||
IL-1β | Canakinumab | 1 | Non-small Cell Lung Cancer | Novartis Pharmaceuticals | NCT03064854 |
IL-1β | Canakinumab | 2 | Melanoma | Novartis Pharmaceuticals | NCT03484923 |
IL-1β | Canakinumab | 3 | Non-small Cell Lung Cancer | Novartis Pharmaceuticals | NCT03631199 |
IL-1β | Genakumab | 1 | Malignant Solid Tumors | GeneScience Pharmaceuticals Co., Ltd | NCT05441046 |
IL-1R | Anakinra | 2 | Multiple Myeloma | Radboud University Medical Center | NCT03233776 |
IL-1R | Anakinra | 2 | Multiple Myeloma | Radboud University Medical Center | NCT04099901 |
IL-1R | Anakinra | 2 | Pancreatic Adenocarcinoma | Baylor Research Institute | NCT04926467 |
IL-1R | Anakinra | 1 | Metastatic Breast Cancer | Baylor Research Institute | NCT01802970 |
IL-1R | Anakinra | 1 | Rectal Cancer | Goethe University | NCT04942626 |
IL-1R | Anakinra | 2 | Metastatic Colorectal Cancer | Centre Georges Francois Leclerc | NCT02090101 |
IL-1R | Anakinra | 1 | Advanced Malignant Neoplasm | M.D. Anderson Cancer Center | NCT01624766 |
Metastatic Malignant Neoplasm | |||||
Recurrent Malignant Neoplasm | |||||
Refractory Malignant Neoplasm | |||||
IL-1R | Anakinra | 1 | Pancreas Cancer | Baylor Research Institute | NCT02021422 |
IL-1R | Anakinra | 2 | Multiple Myeloma and Plasma Cell Neoplasm | Mayo Clinic | NCT00635154 |
IL-1R | Anakinra | 1 | Pancreatic Adenocarcinoma | Baylor Research Institute | NCT02550327 |
IL-1R | Anakinra | 2 | Multiple Myeloma | Radboud University Medical Center | NCT03233776 |
IL-1R | Anakinra | 2 | Pancreatic Adenocarcinoma | Baylor Research Institute | NCT04926467 |
IL-1R | Anakinra | 2 | Diffuse Large B-Cell Lymphoma | Jonsson Comprehensive Cancer Center | NCT04205838 |
IL-1R | Anakinra | High Grade B-Cell Lymphoma | |||
IL-1R | Anakinra | Progressive Disease | |||
IL-1R | Anakinra | Recurrent Diffuse Large B-Cell Lymphoma | |||
IL-1R | Anakinra | 2 | B Cell ALL | Memorial Sloan Kettering Cancer Center | NCT04148430 |
IL-1R | Anakinra | B-Cell Lymphoma | |||
IL-1R | Anakinra | B-cell Non Hodgkin Lymphoma |