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NRAS Q61K - Gene Variant Detail

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Gene NRAS
Variant Q61K
Impact List missense
Protein Effect loss of function - predicted
Gene Variant Descriptions NRAS Q61K is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). Q61K results in activation of downstream pathway signaling, increased survival, and transformation of cultured cells (PMID: 22718121, PMID: 34117033, PMID: 33431353), and is predicted to lead to a loss of Nras protein function based on the effects of HRAS Q61K (PMID: 3510078).
Associated Drug Resistance
Category Variants Paths

NRAS mutant NRAS act mut NRAS Q61K

NRAS mutant NRAS exon3 NRAS Q61X NRAS Q61K

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Transcript NM_002524.5
gDNA chr1:g.114713909G>T
cDNA c.181C>A
Protein p.Q61K
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_002524.4 chr1:g.114713909G>T c.181C>A p.Q61K RefSeq GRCh38/hg38
NM_002524 chr1:g.114713909G>T c.181C>A p.Q61K RefSeq GRCh38/hg38
NM_002524.5 chr1:g.114713909G>T c.181C>A p.Q61K RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF V600E NRAS Q61K melanoma sensitive XL888 Preclinical Actionable In a preclinical study, treatment with XL888 resulted in increased apoptosis and decreased growth of Zelboraf (vemurafenib)-resistant melanoma cells harboring BRAF V600E along with NRAS Q61K in cell culture (PMID: 22351686). 22351686
BRAF V600E NRAS Q61K melanoma resistant Vemurafenib Case Reports/Case Series Actionable In a clinical case study, a melanoma patient harboring BRAF V600E experienced progressive disease after response to treatment Zelboraf (vemurafenib), and was found to have acquired NRAS Q61K (PMID: 34376578). 34376578
BRAF V600E NRAS Q61K melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, a NRAS Q61K mutation conferred resistance to Zelboraf (vemurafenib) in melanoma cells harboring BRAF V600E in culture (PMID: 21107323). 21107323
BRAF V600E NRAS Q61K melanoma resistant Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing NRAS Q61K was resistant to Tafinlar (dabrafenib) in culture (PMID: 36622773). 36622773
BRAF V600E NRAS Q61K melanoma resistant Dabrafenib Preclinical - Pdx Actionable In a preclinical study, a melanoma patient-derived xenograft (PDX) model harboring BRAF V600E and NRAS Q61K was resistant to treatment with Tafinlar (dabrafenib) (PMID: 37729428). 37729428
BRAF V600E NRAS Q61K melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E expressing NRAS Q61K were resistant to Tafinlar (dabrafenib) mediated growth inhibition and retained MEK and ERK signaling (PMID: 22389471). 22389471
BRAF V600E NRAS Q61K melanoma sensitive Dabrafenib + Trametinib Preclinical Actionable In a preclinical study, Talfinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of melanoma cell lines harboring BRAF V600E and NRAS Q61K in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E NRAS Q61K melanoma sensitive Dabrafenib + Trametinib Preclinical - Pdx Actionable In a preclinical study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) moderately inhibited tumor growth in a melanoma patient-derived xenograft (PDX) model harboring BRAF V600E and NRAS Q61K (PMID: 37729428). 37729428
BRAF V600E NRAS Q61K lung adenocarcinoma predicted - resistant Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, a breast cancer patient with metastatic lung adenocarcinoma harboring BRAF V600E developed progressive disease after initial response to Talfinlar (dabrafenib) and Mekinist (trametinib) combination therapy, NRAS Q61K was identified as an acquired mutation after disease progression (PMID: 29631033). 29631033
BRAF V600E NRAS Q61K colorectal cancer predicted - resistant Panitumumab + Vemurafenib Case Reports/Case Series Actionable In a clinical case study, a patient with BRAF V600E colorectal cancer developed progressive disease after a partial response lasting 40 weeks to Vectibix (panitumumab) and Zelboraf (vemurafenib) combination treatment, NRAS Q61K was identified as an acquired mutation at the time of progression (PMID: 28951457). 28951457
BRAF V600E NRAS Q61K melanoma sensitive ASTX029 Preclinical - Cell culture Actionable In a preclinical study, ASTX029 treatment reduced Erk and Rsk phosphorylation and inhibited growth of a melanoma cell line harboring BRAF V600E and expressing NRAS Q61K in culture (PMID: 34330842). 34330842
BRAF V600E NRAS Q61K melanoma resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing NRAS Q61K was resistant to Mekinist (trametinib) in culture (PMID: 36622773). 36622773
BRAF V600E NRAS Q61K melanoma predicted - resistant DS03090629 Preclinical - Cell culture Actionable In a preclinical study, DS03090629 inhibited Erk but not Mek phosphorylation and did not inhibit proliferation in a melanoma cell line harboring BRAF V600E and expressing NRAS Q61K in culture (PMID: 36622773). 36622773
BRAF V600E NRAS Q61K melanoma sensitive Encorafenib + Talazoparib Preclinical - Patient cell culture Actionable In a preclinical study, treatment with the combination of Talzenna (talazoparib) and Braftovi (encorafenib) synergistically inhibited viability of patient-derived melanoma spheroids harboring BRAF V600E and NRAS Q61K in culture (PMID: 37729428). 37729428
BRAF V600E NRAS Q61K melanoma sensitive Encorafenib + Olaparib Preclinical - Patient cell culture Actionable In a preclinical study, treatment with the combination of Lynparza (olaparib) and Braftovi (encorafenib) synergistically inhibited viability of patient-derived melanoma spheroids harboring BRAF V600E and NRAS Q61K in culture (PMID: 37729428). 37729428
BRAF V600E NRAS Q61K melanoma sensitive Encorafenib + Rucaparib Preclinical - Patient cell culture Actionable In a preclinical study, treatment with the combination of Rubraca (rucaparib) and Braftovi (encorafenib) synergistically inhibited viability of patient-derived melanoma spheroids harboring BRAF V600E and NRAS Q61K in culture (PMID: 37729428). 37729428
BRAF V600E NRAS Q61K melanoma sensitive Dabrafenib + Talazoparib Preclinical - Patient cell culture Actionable In a preclinical study, treatment with the combination of Talzenna (talazoparib) and Tafinlar (dabrafenib) synergistically inhibited viability of patient-derived melanoma spheroids harboring BRAF V600E and NRAS Q61K in culture (PMID: 37729428). 37729428
BRAF V600E NRAS Q61K melanoma sensitive Dabrafenib + Talazoparib + Trametinib Preclinical - Pdx Actionable In a preclinical study, treatment with the combination of Talzenna (talazoparib), Tafinlar (dabrafenib), and Mekinist (trametinib) inhibited tumor growth and improved survival compared to controls in a melanoma patient-derived xenograft (PDX) model harboring BRAF V600E and NRAS Q61K (PMID: 37729428). 37729428
BRAF V600E NRAS Q61K melanoma sensitive Talazoparib Preclinical - Pdx Actionable In a preclinical study, Talzenna (talazoparib) treatment inhibited tumor growth and led to improved survival compared to controls in a melanoma patient-derived xenograft (PDX) model harboring BRAF V600E and NRAS Q61K (PMID: 37729428). 37729428
BRAF V600E NRAS Q61K papillary thyroid carcinoma predicted - resistant Vemurafenib Case Reports/Case Series Actionable In a clinical case study, NRAS Q61K was identified on post-progression biopsy in a patient with metastatic papillary thyroid carcinoma harboring BRAF V600E, who previously responded to Zelboraf (vemurafenib) treatment (PMID: 30036146). 30036146
BRAF V600E NRAS Q61K lung non-small cell carcinoma predicted - sensitive PF-07799933 Preclinical - Biochemical Actionable In a preclinical study, PF-07799933 inhibited Erk phosphorylation in melanoma cells harboring BRAF V600E and NRAS Q61K in culture (PMID: 38691346). 38691346
CDKN2A loss NRAS Q61K melanoma sensitive Palbociclib + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Ibrance (palbociclib) and Mekinist (trametinib) induced tumor regression in a mouse melanoma model expressing NRAS Q61K and harboring CDKN2A loss (PMID: 22983396). 22983396
CDKN2A loss NRAS Q61K melanoma sensitive SBI-0640756 Preclinical Actionable In a preclinical study, SBI-0640756 delayed tumor growth of melanomas in mice with a genetic background of NRAS Q61K and CDKN2A loss (PMID: 26603897). 26603897
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were resistant to Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were resistant to growth inhibition by Zelboraf (vemurafenib) in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma decreased response Trametinib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were >20-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma decreased response GSK2126458 Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma conflicting Dabrafenib + GSK2126458 Preclinical Actionable In a preclinical study, the response of human melanoma cell lines harboring BRAF V600E, NRAS Q61K, and MAP2K1 P387S to Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) was conflicting as one cell line with this mutation profile responded to the combination and another cell line with the mutation profile did not (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma sensitive GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E, NRAS Q61K, and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S were resistant Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, A146T and MAP2K1 P387S were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T melanoma resistant Trametinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S were resistant to growth inhibition by Mekinist (trametinib) in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T melanoma decreased response GSK2126458 Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T melanoma sensitive GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600K NRAS Q61K melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600K and NRAS Q61K were resistant to Tafinlar (dabrafenib) growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600K NRAS Q61K melanoma decreased response Trametinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600K and NRAS Q61K were 3-7 fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600K in culture (PMID: 22389471). 22389471
BRAF V600K NRAS Q61K melanoma predicted - sensitive GSK2126458 Preclinical - Cell culture Actionable In a preclinical study, Omipalisib (GSK2126458) inhibited the growth of melanoma cell lines harboring BRAF V600K with NRAS Q61K in culture (PMID: 22389471). 22389471
BRAF V600K NRAS Q61K melanoma sensitive Dabrafenib + Trametinib Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) in combination with Mekinist (trametinib) inhibited growth of melanoma cell lines harboring BRAF V600K and NRAS Q61K in culture (PMID: 22389471). 22389471
BRAF V600K NRAS Q61K melanoma sensitive GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600K and NRAS Q61K in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600K NRAS Q61K melanoma sensitive Dabrafenib + GSK2126458 Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600K and NRAS Q61K in culture (PMID: 22389471). 22389471
BRAF V600E NRAS Q61K NRAS A146T melanoma sensitive Dabrafenib + Trametinib Preclinical Actionable In a preclinical study, Talfinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of human melanoma cells harboring BRAF V600E and NRAS A146T and NRAS Q61K in culture (PMID: 22389471). 22389471
BRAF G469R NRAS Q61K melanoma sensitive LY3009120 Preclinical Actionable In a preclinical study, LY3009120 inhibited soft agar growth of human melanoma cancer cells harboring BRAF G469R and NRAS Q61K in culture (PMID: 26343583). 26343583
BRAF G469R NRAS Q61K melanoma decreased response Selumetinib Preclinical Actionable In a preclinical study, Selumetinib (AZD6244) modestly inhibited proliferation of human melanoma cells harboring BRAF G469R and NRAS Q61K in culture (PMID: 26343583). 26343583
BRAF G469R NRAS Q61K melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, human melanoma cells harboring BRAF G469R and NRAS Q61K were insensitive to Zelboraf (vemurafenib) in culture (PMID: 26343583). 26343583
BRAF V600X BRAF amp NRAS Q61K melanoma resistant Vemurafenib Clinical Study - Cohort Actionable In a clinical study, a melanoma patient harboring a BRAF V600 mutation developed resistant mutations, BRAF amplification and NRAS Q61K, during treatment with Zelboraf (vemurafenib) (PMID: 24265153). 24265153
BRAF wild-type NRAS Q61K melanoma resistant GDC0879 Preclinical - Pdx Actionable In a preclinical study, GDC0879 failed to inhibit growth of BRAF wild-type melanoma cells harboring NRAS Q61K in patient-derived xenograft models (PMID: 19276360). 19276360
BRAF L597V NRAS Q61K lung non-small cell carcinoma sensitive AZ628 Preclinical - Cell culture Actionable In a preclinical study, AZ628 inhibited proliferation of non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K in culture (PMID: 27523909). 27523909
BRAF L597V NRAS Q61K lung non-small cell carcinoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K in culture (PMID: 27523909). 27523909
BRAF L597V NRAS Q61K lung non-small cell carcinoma decreased response PLX7904 Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K demonstrated decreased sensitivity to PLX7904 in culture (PMID: 27523909). 27523909
BRAF L597V NRAS Q61K lung non-small cell carcinoma decreased response Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). 27523909
BRAF L597V NRAS Q61K lung non-small cell carcinoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 27523909). 27523909
BRAF L597V NRAS Q61K lung non-small cell carcinoma sensitive IHMT-RAF-128 Preclinical - Cell culture Actionable In a preclinical study, IHMT-RAF-128 inhibited proliferation in a non-small cell lung cancer cell line harboring NRAS Q61K and BRAF L597V in culture (PMID: 37164118). 37164118
BRAF G466V NRAS Q61K lung non-small cell carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) growth of a non-small cell lung cancer cell line harboring BRAF G466V and expressing NRAS Q61K in culture (PMID: 28783719). 28783719
KEAP1 loss NRAS Q61K lung cancer decreased response Trametinib Preclinical - Cell culture Actionable In a preclinical study, KEAP1 knockout resulted in decreased sensitivity to Mekinist (trametinib) in a lung cancer cell line harboring NRAS Q61K in culture (PMID: 28145866). 28145866
BRAF G469V NRAS Q61K melanoma sensitive Encorafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). 29903896
BRAF G469V NRAS Q61K melanoma sensitive Binimetinib + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mektovi (binimetinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). 29903896
BRAF G469V NRAS Q61K melanoma predicted - resistant Trametinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the addition of Zelboraf (vemurafenib) to treatment with Mekinist (trametinib) resulted in increased proliferation compared to Mekinist (trametinib) alone in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). 29903896
BRAF G469V NRAS Q61K melanoma sensitive LY3009120 Preclinical - Cell culture Actionable In a preclinical study, LY3009120 inhibited growth of a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). 29903896
BRAF G469V NRAS Q61K melanoma no benefit Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, Tafinlar (dabrafenib) treatment did not result in significant growth inhibition in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). 29903896
ATM T1200Lfs*7 NRAS Q61K TP53 R213* sarcoma predicted - resistant Olaparib Case Reports/Case Series Actionable In a clinical case study, Lynparza (olaparib) treatment resulted in rapid disease progression in a patient with high-grade sarcoma harboring ATM T1200Lfs*7, NRAS Q61K, and TP53 R213* (PMID: 29304353). 29304353
NRAS Q61K NRAS mut melanoma predicted - resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61K demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 30819666). 30819666
NRAS Q61K NRAS mut melanoma predicted - resistant Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61K demonstrated resistance to the combination treatment of Mekinist (trametinib) and Ibrance (palbociclib) in culture (PMID: 30819666). 30819666
NRAS Q61K NRAS mut melanoma decreased response Palbociclib Preclinical - Cell culture Actionable In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61K demonstrated a decreased response to treatment with Ibrance (palbociclib) in culture compared to control (PMID: 30819666). 30819666
BRAF D287H NRAS Q61K melanoma predicted - sensitive LXH 254 Preclinical - Cell line xenograft Actionable In a preclinical study, a melanoma cell line harboring BRAF D287H and NRAS Q61K was sensitive to treatment with LXH254, demonstrating inhibition of cell proliferation in culture, and inhibition of tumor growth in a cell line xenograft model of melanoma (PMID: 33355204). 33355204
BRAF loss NRAS Q61K melanoma decreased response LXH 254 Preclinical - Cell culture Actionable In a preclinical study, CRISPR-Cas9 mediated knockout of BRAF in a melanoma cell line harboring NRAS Q61K led to decreased sensitivity to LXH254 treatment compared to parental cells harboring BRAF D287H and NRAS Q61K in culture (PMID: 33355204). 33355204
BRAF L597Q FGFR2 H167_N173del FGFR2 N550K FGFR2 L618F NRAS Q61K intrahepatic cholangiocarcinoma predicted - resistant LY3214996 Case Reports/Case Series Actionable In a clinical case study, acquired NRAS Q61K and FGFR2 N550K mutations were identified following progression on LY3214996 in an intrahepatic cholangiocarcinoma patient harboring BRAF L597Q, FGFR2 H167_N173del, and FGFR2 L618F (PMID: 33926920). 33926920
BRAF V600E CDKN2A loss NRAS Q61K melanoma predicted - resistant Cobimetinib + Vemurafenib Case Reports/Case Series Actionable In a clinical case study, a melanoma patient harboring BRAF V600E and NRAS Q61K experienced progressive disease after a response to combination therapy with Zelboraf (vemurafenib) and Cotellic (cobimetinib), land was found to have acquired loss of CDKN2A (PMID: 34376578). 34376578
FLT3 exon 14 ins NRAS Q61K acute myeloid leukemia resistant FF-10101 Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3-ITD mutation and expressing NRAS Q61K demonstrated resistance to treatment with FF-10101 in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins NRAS Q61K acute myeloid leukemia resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3-ITD mutation and expressing NRAS Q61K demonstrated resistance to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins NRAS Q61K acute myeloid leukemia resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3-ITD mutation and expressing NRAS Q61K demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins NRAS Q61K acute myeloid leukemia resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring FLT3-ITD and NRAS Q61K were resistant to Xospata (gilteritinib) as demonstrated by increased cell growth and RAS/MAPK pathway activation in culture (PMID: 31088841). 31088841
FLT3 exon 14 ins NRAS Q61K acute myeloid leukemia predicted - sensitive FF-10101 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of FF-10101 and Mekinist (trametinib) resulted in decreased viability of acute myeloid leukemia cells harboring a FLT3-ITD mutation and expressing NRAS Q61K compared to treatment with FF-10101 alone in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins NRAS Q61K acute myeloid leukemia sensitive Gilteritinib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Xospata (gilteritinib) and Mekinist (trametinib) inhibited cell growth in acute myeloid leukemia cells harboring FLT3-ITD and NRAS Q61K in culture (PMID: 31088841). 31088841
FLT3 exon 14 ins NRAS Q61K acute myeloid leukemia resistant RMC-4550 Preclinical - Cell culture Actionable In a preclinical study, an acute myeloid leukemia cell line harboring FLT3 ITD and expressing NRAS Q61K was resistant to RMC-4550 treatment in culture (PMID: 37992684). 37992684
FLT3 exon 14 ins NRAS Q61K acute myeloid leukemia resistant Gilteritinib + RMC-4550 Preclinical - Cell culture Actionable In a preclinical study, an acute myeloid leukemia cell line harboring FLT3 ITD and NRAS Q61K was resistant to the combination of RMC-4550 and Xospata (gilteritinib) in culture (PMID: 37992684). 37992684
NRAS Q61K PIK3CA E545K melanoma predicted - resistant Binimetinib + Ribociclib Preclinical - Cell line xenograft Actionable In a preclinical study, a melanoma cell line harboring NRAS Q61K and expressing PIK3CA E545K was resistant to combination treatment with Mektovi (binimetinib) and Kisqali (ribociclib) in culture and in a cell line xenograft model, demonstrating lack of tumor regression and continued tumor growth (PMID: 29496665). 29496665
NRAS Q61K PIK3CA E545K melanoma predicted - sensitive Ribociclib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring NRAS Q61K and expressing PIK3CA E545K was resistant to treatment with Kisqali (ribociclib) in culture (PMID: 29496665). 29496665
NRAS Q61K PIK3CA E545K melanoma predicted - resistant Binimetinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring NRAS Q61K and expressing PIK3CA E545K was resistant to treatment with Mektovi (binimetinib) in culture (PMID: 29496665). 29496665
NRAS Q61K PIK3CA E545K melanoma predicted - sensitive Binimetinib + PF-4708671 + Ribociclib Preclinical - Cell line xenograft Actionable In a preclinical study, the addition of PF-4708671 resensitized a melanoma cell line harboring NRAS Q61K and expressing PIK3CA E545K to combination treatment with Mektovi (binimetinib) and Kisqali (ribociclib) in culture, resulting in inhibition of cell growth, and resulted in tumor regression and complete responses in cell line xenograft models (PMID: 29496665). 29496665
NRAS Q61K PIK3CA E545K melanoma predicted - sensitive Binimetinib + Ribociclib + Sirolimus Preclinical - Cell culture Actionable In a preclinical study, the addition of Sirolimus (rapamycin) resensitized a melanoma cell line harboring NRAS Q61K and expressing PIK3CA E545K to combination treatment with Mektovi (binimetinib) and Kisqali (ribociclib) in culture, resulting in inhibition of cell growth (PMID: 29496665). 29496665
FLT3 exon 14 ins FLT3 D835X NRAS Q61K acute myeloid leukemia predicted - resistant Gilteritinib Case Reports/Case Series Actionable In a clinical study, two patients with acute myeloid leukemia harboring FLT3-ITD and a D835 mutation progressed on Xospata (gilteritinib) treatment and were found to have acquired NRAS Q61K (PMID: 31088841). 31088841
ALK F1174L NRAS Q61K neuroblastoma resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, expression of NRAS Q61K in a neuroblastoma cell line harboring ALK F1174L conferred resistance to Zykadia (ceritinib) in culture (PMID: 35689207). 35689207
ALK F1174L NRAS Q61K neuroblastoma resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, expression of NRAS Q61K in a neuroblastoma cell line harboring ALK F1174L conferred resistance to Lorbrena (lorlatinib) in culture (PMID: 35689207). 35689207
FGFR2 L262_A266delinsD NRAS Q61K cholangiocarcinoma predicted - resistant Futibatinib Case Reports/Case Series Actionable In a retrospective analysis, a cholangiocarcinoma patient harboring FGFR2 L262_A266delinsD progressed on treatment with Lytgobi (futibatinib) and was found to have acquired NRAS Q61K via cell-free DNA (PMID: 39706336; NCT02052778). 39706336
FGFR2 rearrange NRAS Q61K cholangiocarcinoma predicted - resistant Pemigatinib Case Reports/Case Series Actionable In a retrospective analysis, a cholangiocarcinoma patient harboring an FGFR2 rearrangement progressed on treatment with Pemazyre (pemigatinib) and was found to have acquired NRAS Q61K via cell-free DNA (PMID: 39706336). 39706336