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A DNA-unwinding enzyme that mismatch-repair-deficient cancers cannot live without; the first WRN inhibitors are in trials as a chemotherapy-free option for MSI-high tumours that fail immunotherapy. This dossier gathers the 2 products (0 approved), 2 trials, 2 pathways and 0 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
RecQ family 3'→5' DNA helicase and exonuclease; germline loss causes Werner progeroid syndrome; in MSI cancers its helicase (not exonuclease) activity prevents replication fork collapse at expanded (TA)n repeats.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Endometrial cancer | 30% | MSI-H | ||
| Gastric & gastro-oesophageal junction cancer | 20% | MSI-H | ||
| Colorectal cancer | 15% | MSI-H (WRN-dependent) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
| Modality | Phase 2 |
|---|---|
| Small molecule 2 |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
| 1/2 | Recruiting | A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of NDI-219216 in Patients With Advanced Solid Tumors With/Without Microsatellite Instability and/or Deficient Mismatch Repair | - | ||
| 1/2 | Recruiting | A Multicenter, Multi-Part, Phase 1/2 Study of EIK1005 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors, Including Checkpoint Inhibitor Naïve Participants With Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) Tumors | - |
No recorded escape route names this target.
After DNA is copied, a proofreading crew fixes the letters the polymerase got wrong. Lose it and the genome fills with thousands of small errors, especially in repetitive stretches (microsatellites). Those errors make abnormal proteins that the immune system can see, which is why immunotherapy works so well in these cancers.
Which nodes have drugs →Two genes are synthetically lethal when losing either alone is fine but losing both kills the cell. Cancers that have already lost one (a tumour suppressor you cannot put back) become uniquely dependent on the other, which you can drug. BRCA and PARP was the first proof; a dozen more pairs are now in trials.
Which nodes have drugs →No companion diagnostic in the registry measures this target.
No model entry for this target yet; check the cancer entries on the models page.
No open questions recorded for this target yet. Suggest one.
Query for this target: (TITLE:"WRN helicase" OR ABSTRACT:"WRN helicase" OR TITLE:"MSI-high cancers" OR ABSTRACT:"MSI-high cancers" OR TITLE:"WRN" OR ABSTRACT:"WRN") 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 WRN helicase (MSI-high cancers), not a curated reading list.
The dossier as machine-readable JSON, at /api/v1/dossiers/wrn.json: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/wrn.json. Licence CC BY-NC 4.0.