PRMT5 (MTAP-deleted cancers)
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.
Homozygous deletion of MTAP (co-deleted with CDKN2A on 9p21) causes accumulation of MTA, which partially inhibits PRMT5, leaving MTAP-null cells hypersensitive to further PRMT5 inhibition. MTA-cooperative PRMT5 inhibitors (AMG 193, MRTX1719/BMS-986504, TNG908, TNG462, AZD3470) exploit this synthetic lethality with a wide therapeutic window compared with first-generation PRMT5 inhibitors (which caused thrombocytopenia). Responses have been reported in MTAP-deleted NSCLC, mesothelioma, pancreatic and biliary cancers; combination with KRAS G12C inhibitors is being tested and phase 3 trials began in 2025-26. MTAP deletion occurs in ~40% of mesothelioma and glioblastoma, ~20% of pancreatic cancer and bladder cancer, ~15% of NSCLC.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
No product in this corpus aims at PRMT5 (MTAP-deleted cancers) yet. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
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.
- Mesothelioma (~40% MTAP deletion)
- Glioblastoma (~40%)
- Pancreatic adenocarcinoma (~20%)
- Urothelial carcinoma (~20%)
- NSCLC (~15%)
- Cholangiocarcinoma, melanoma, sarcoma (subsets)
How common it is, by cancer
| 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.
Latest papers
topQuery 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.
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