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|Gene Variant Descriptions||NRAS Q61X indicates any NRAS missense mutation that results in replacement of the glutamine (Q) at amino acid 61 by a different amino acid. NRAS codon 61 mutations are hotspot mutations that often result in a loss of Nras GTPase activity and activation of downstream pathways (PMID: 27664710, PMID: 28666118, PMID: 22589270, PMID: 26985062).|
|Associated Drug Resistance|
|Category Variants Paths||
NRAS mutant NRAS exon3 NRAS Q61X
|Transcript||gDNA||cDNA||Protein||Source Database||Genome Build|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|NRAS Q61X||myelodysplastic syndrome||not applicable||N/A||Guideline||Prognostic||NRAS Q61X is associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org).||detail...|
|NRAS Q61X||colorectal cancer||resistant||Cetuximab||FDA contraindicated||Actionable||Erbitux (cetuximab) treatment of colorectal cancer patients with NRAS exon 3, codon 61 mutations is contraindicated (FDA.gov).||detail...|
|NRAS Q61X||colorectal cancer||resistant||Panitumumab||FDA contraindicated||Actionable||Vectibix (panitumumab) treatment of colorectal cancer patients with NRAS exon 3, codon 61 mutations is contraindicated (FDA.gov).||detail...|
|NRAS Q61X||Advanced Solid Tumor||unknown||Binimetinib||Phase II||Actionable||In a Phase II trial (MATCH), Mektovi (binimetinib) therapy led to a nonpromising objective response rate of 2.1% (1/47) in patients (pts) with advanced solid tumors harboring NRAS G12/13 or Q61 mutations, Q61-mutant pts achieved longer overall survival (13.1 vs 5.5 mo, p=0.04) and progression-free survival (5.8 vs 1.8 mo, p=0.006) compared to G12/13-mutant pts examining all tumor types, but not when colorectal caner was excluded (HR 0.84, p=0.70; HR 0.67, p=0.4, respectively) (PMID: 33637626; NCT02465060).||33637626|
|NRAS Q61X||colorectal cancer||unknown||Binimetinib||Phase II||Actionable||In a Phase II trial (MATCH), Mektovi (binimetinib) treatment did not demonstrate promising efficacy in patients with advanced solid tumors harboring NRAS mutations at codon 12 (n=17), 13 (n=8), or 61 (n=22), however, colorectal cancer patients harboring NRAS Q61 mutations (n=8) achieved longer overall survival (HR 0.34, p=0.03) and progression-free survival (HR 0.23, p=0.007) compared to those harboring mutations at G12 or G13 (n=16) (PMID: 33637626; NCT02465060).||33637626|
|NRAS Q61X||melanoma||sensitive||Binimetinib + Ribociclib||Phase Ib/II||Actionable||In a Phase Ib/II trial, Kisqali (ribociclib) plus Mektovi (binimetinib) was well tolerated in NRAS-mutant melanoma patients and resulted in an overall response rate (ORR) of 19.5% (8/41; all PR), disease control rate of 70.7% (29/41), median duration of response of 10.3 months, median progression-free survival of 3.7 months, and median overall survival (OS) of 11.3 months in the phase II cohort, and a response rate of 22.9% (16/70) in patients with an NRAS Q61 mutation overall (PMID: 35294522; NCT01781572).||35294522|