Molecular Profile Detail

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Profile Name BRAF V600E NRAS Q61K
Gene Variant Detail

BRAF V600E (gain of function)

NRAS Q61K (loss of function - predicted)

Relevant Treatment Approaches

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches 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 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 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 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 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 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 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 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 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 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 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 thyroid gland papillary 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