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An enzyme that cancers lacking the MTAP gene (about 10-15% of all tumours) depend on more than normal cells do; new inhibitors designed to exploit that difference are in late trials. This dossier gathers the 5 products (0 approved), 11 trials, 1 pathway 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.
Type II protein arginine methyltransferase forming symmetric dimethylarginine on histones (H4R3, H3R8) and splicing factors (SmD3); essential for spliceosome function; MTA is a competitive SAM-site inhibitor accumulating when MTAP is lost.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Mesothelioma | 40% | MTAP homozygous deletion | ||
| Glioma & glioblastoma | 40% | MTAP deletion | ||
| Pancreatic ductal adenocarcinoma | 20% | MTAP deletion | ||
| Non-small-cell lung cancer | 15% | MTAP deletion |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
| Modality | Phase 3 | Phase 2 |
|---|---|---|
| Small molecule 5 |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
| 2/3 | Active | A Randomized, Phase 2/3 Study Comparing Navlimetostat (BMS-986504) in Combination With Nab-paclitaxel and Gemcitabine Versus Placebo in Combination With Nab-paclitaxel and Gemcitabine in Participants With Untreated Metastatic Pancreatic Ductal Adenocarcinoma Harboring Homozygous MTAP Deletion | - | ||
| 2/3 | Recruiting | A Randomized Phase 2/3 Study of Navlimetostat (BMS-986504) in Combination With Pembrolizumab and Chemotherapy Versus Placebo Plus Pembrolizumab and Chemotherapy in First-line Metastatic Non-small Cell Lung Cancer Participants With Homozygous MTAP Deletion | - | ||
| 2 | Active | A Phase 2 Study Evaluating the Efficacy, Safety, Tolerability, and Pharmacokinetics of Anvumetostat in Subjects With Methylthioadenosine Phosphorylase (MTAP)-Deleted Previously Treated Advanced Non-Small Cell Lung Cancer (NSCLC) | - | ||
| 2 | Recruiting | A Phase II Study Evaluating BMS-986504 in MTAP-deleted Pancreatic Cancer | - | ||
| 1/2 | Active | A Phase 1/1b/2 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Anvumetostat Alone and in Combination With Docetaxel in Subjects With Advanced MTAP-null Solid Tumors | - | ||
| 1/2 | Recruiting | PRIMROSE: A Modular Phase I/IIa, Multi-centre, Dose Escalation, and Expansion Study of AZD3470, a MTA Cooperative PRMT5 Inhibitor, as Monotherapy and in Combination With Anticancer Agents in Participants With Advanced/Metastatic Solid Tumors That Are MTAP Deficient | - | ||
| 1/2 | Recruiting | A Modular Phase I/II, Open-label, Multicentre Study to Evaluate the Safety, Tolerability, and Efficacy of AZD3470, a PRMT5 Inhibitor, as Monotherapy or in Combination With Anticancer Agent(s) in Participants With Haematologic Malignancies | - | ||
| 1/2 | Active | A Phase 1/2, Open-label, Multicenter Clinical Trial Investigating the Safety, Tolerability, Pharmacokinetics, and Antineoplastic Activity of S095035 (MAT2A Inhibitor) as a Single Agent and in Combination in Adult Participants With Advanced or Metastatic Solid Tumors With Homozygous Deletion of MTAP | - | ||
| 1/2 | Recruiting | A Phase 1/2, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, and Preliminary Antitumor Activity of TNG456 Monotherapy and in Combination With Abemaciclib in Patients With Solid Tumors With MTAP Loss | - | ||
| 1/2 | Recruiting | A Phase 1/2, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, and Preliminary Anti-tumor Activity of TNG462 as a Single Agent and in Combination in Patients With MTAP-deleted Advanced or Metastatic Solid Tumors | - | ||
| 1/2 | Recruiting | A Phase 1/2, Multicenter, Open-Label Study to Evaluate Safety, Tolerability & Antitumor Activity of TNG462 in Combination With Other Agents in Patients With Pancreatic Cancer With MTAP Loss and Pancreatic or Non-Small Cell Lung Cancer With MTAP Loss & RAS Mutation | - |
No recorded escape route names this target.
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:"PRMT5" OR ABSTRACT:"PRMT5" OR TITLE:"MTAP-deleted cancers" OR ABSTRACT:"MTAP-deleted cancers") 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 PRMT5 (MTAP-deleted cancers), not a curated reading list.
The dossier as machine-readable JSON, at /api/v1/dossiers/prmt5-mtap.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/prmt5-mtap.json. Licence CC BY-NC 4.0.