CASP8
CASP8 (Caspase-8) is an enzyme. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Head and neck squamous cell carcinoma, Skin cancer, Cervical cancer and 5 more.
Overview
Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic development and adulthood. Initiator protease that induces extrinsic apoptosis by mediating cleavage and activation of effector caspases responsible for FAS/CD95-mediated and TNFRSF1A-induced cell death. Cleaves and activates effector caspases CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10.
CIViC holds 2 clinical evidence items and 0 assertions across 2 variants, naming Conatumumab. Open Targets scores its association with cancer at 0.82 (direct and indirect evidence; datatypes literature 0.99, animal model 0.49, genetic association 0.70, somatic mutation 0.93). IntOGen calls it a driver in 17 cohorts (2 activating, 15 loss-of-function), covering Basal Cell Carcinoma, Bladder Urothelial Carcinoma, Invasive Breast Carcinoma, Cervical Adenocarcinoma, Cervical Squamous Cell Carcinoma, Cutaneous Squamous Cell Carcinoma and others.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · CASP8 (Caspase-8) is an enzyme. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Head and neck squamous cell carcinoma, Skin cancer, Cervical cancer and 5 more.
- 1 · What it is
CASP8 (Caspase-8) is an enzyme. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Head and neck squamous cell carcinoma, Skin cancer, Cervical cancer and 5 more.
- 2 · What goes wrong in cancer
Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic development and adulthood.
- 3 · How drugs use it
No product in this corpus aims at CASP8 yet. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
External identifiers
Sources: HGNC HGNC:1509 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q14790 (protein name, function text, keywords and locations (REST API)); CIViC gene CASP8 (2 evidence items, 0 assertions, 2 variants; diseases: Neuroblastoma, Ewing Sarcoma Of Bone (GraphQL API, CC0)); Open Targets ENSG00000064012 (association with cancer (MONDO_0004992) 0.82; per-cancer scores at or above 0.5: colorectal cancer 0.55, ovarian cancer 0.56, melanoma 0.57, head and neck squamous cell carcinoma 0.66, skin cancer 0.63, basal cell carcinoma 0.52 (GraphQL API, CC0)); IntOGen CASP8 (driver in 17 cohorts (Act 2, LoF 15); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic development and adulthood. Initiator protease that induces extrinsic apoptosis by mediating cleavage and activation of effector caspases responsible for FAS/CD95-mediated and TNFRSF1A-induced cell death. Cleaves and activates effector caspases CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10. Binding to the adapter molecule FADD recruits it to either receptor FAS/TNFRSF6 or TNFRSF1A. The resulting aggregate called the death-inducing signalling complex (DISC) performs CASP8 proteolytic activation. The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases. Location: Cytoplasm; Nucleus; Cell projection, lamellipodium (UniProt). Locus 2q33.1 (HGNC).
- Head and neck squamous cell carcinoma: Open Targets association 0.66 with head and neck squamous cell carcinoma (MONDO_0010150); IntOGen driver in 4 cohorts (HNSC)
- Skin cancer: Open Targets association 0.63 with skin cancer (MONDO_0002898)
- Cervical cancer: IntOGen driver in 3 cohorts (CEAD, CESC)
- Breast cancer: Open Targets association 0.58 with breast cancer (MONDO_0007254); IntOGen driver in 2 cohorts (BRCA)
- Nasopharyngeal carcinoma: IntOGen driver in 2 cohorts (NPC)
- Bladder & urothelial cancer: IntOGen driver in 1 cohort (BLCA)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 1 therapies; IntOGen calls it an activating (Act) driver in 2 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 15 cohorts; CIViC holds 2 clinical evidence items on its variants. Evidence tier "clinical-evidence" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
- Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Ewing Sarcoma Of Bone.
Latest papers
topQuery for this target: (TITLE:"CASP8" OR ABSTRACT:"CASP8" OR TITLE:"caspase 8" OR ABSTRACT:"caspase 8" OR TITLE:"Caspase-8" OR ABSTRACT:"Caspase-8" OR TITLE:"MCH5" OR ABSTRACT:"MCH5" OR TITLE:"FLICE" OR ABSTRACT:"FLICE" OR TITLE:"Casp-8" OR ABSTRACT:"Casp-8") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about CASP8, not a curated reading list.
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