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NRAS is one of the three RAS switch proteins that pass growth signals into the cell. When a mutation jams it on, as in a share of melanomas, the cell keeps dividing; today's drugs reach it indirectly through MEK or RAF, and pan-RAS inhibitors that bind the active form are in trials. This dossier gathers the 1 product (0 approved), 3 trials, 0 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.
RAS proteins share the GDP/GTP cycle and intrinsic GTPase activity; neurofibromin (NF1) stimulates that hydrolysis and so switches RAS off (UniProt P21359). Mutant NRAS stays GTP-bound, so the corpus drugs act below it (tunlametinib on MEK, naporafenib on RAF) or on the active state of all RAS isoforms (JYP0015). The lenzilumab record notes that chronic myelomonocytic leukaemia progenitors with NRAS, KRAS or CBL mutations proliferate in response to very low GM-CSF levels.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Colorectal cancer | 4-9% | Activating mutation (codon 12, 13, 59, 61 or 117) | cBioPortal: 298 of 7,237, 4.1%, in crc_msk_2026; 46 of 1,134, 4.1%, in crc_msk_2017; 66 of 1,516, 4.4%, in crc_eo_2020; 33 of 534, 6.2%, in coadread_tcga_pan_can_atlas_2018; 20 of 224, 8.9%, in coadread_tcga_pub; 27 of 619, 4.4%, in coadread_dfci_2016; 24 of 1,015, 2.4%, in crc_sysucc_2022. NRAS runs the other way from KRAS on codon usage: in crc_msk_2026 the missense records split 137 at codons 59 and 61 against 123 at codons 12 and 13, with Q61K the single commonest allele (63 records), then G12D (54), Q61R (40) and Q61L (20) (cBioPortal). | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
| Modality | Phase 2 |
|---|---|
| Small molecule 1 |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
PRIME NCT00364013 | 3 | Positive | Previously untreated metastatic colorectal cancer: FOLFOX4 with or without panitumumab, analysed by extended RAS status | In RAS wild-type disease, overall survival 26.0 against 20.2 months (hazard ratio 0.78); patients with non-exon-2 RAS mutations did worse with panitumumab. | |
CHRONOS NCT03227926 | 2 | Positive | RAS wild-type metastatic colorectal cancer that had already progressed on an EGFR antibody: a blood test for RAS, BRAF and EGFR resistance mutations decides who is rechallenged with panitumumab alone | Objective response 30 percent (8 of 27) and disease control 63 percent in ctDNA-selected patients; 31 percent of those screened were excluded by a resistance mutation. | |
| 2 | Recruiting | A Multi-center, Open-label, Phase I/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of JYP0015 in Advanced Solid Tumors With RAS Mutation | - |
No recorded escape route names this target.
No pathway diagram carries this target as a node.
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:"NRAS" OR ABSTRACT:"NRAS" OR TITLE:"N-ras" OR ABSTRACT:"N-ras" OR TITLE:"NRAS proto-oncogene, GTPase" OR ABSTRACT:"NRAS proto-oncogene, GTPase") 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 NRAS, not a curated reading list.
The dossier as machine-readable JSON, at /api/v1/dossiers/nras.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/nras.json. Licence CC BY-NC 4.0.