Molecular Profile Detail

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Profile Name MAP2K1 C121S
Gene Variant Detail

MAP2K1 C121S (gain of function)

Relevant Treatment Approaches

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF V600E MAP2K1 C121S melanoma sensitive E6201 Preclinical Actionable In a preclinical study, E6201 inhibited Mapk pathway activation and proliferation of melanoma cell line harboring BRAF V600E mutation and overexpressing MAP2K1 C121S in culture (PMID: 24448821). 24448821
BRAF V600E MAP2K1 C121S melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, expression of MAP2K1 C121S conferred resistance to Zelboraf (vemurafenib) in melanoma cell lines harboring BRAF V600E, resulting in decreased sensitivity to Zelboraf (vemurafenib)-induced inhibition of MAPK pathway activation and cell proliferation in culture (PMID: 24448821). 24448821
BRAF V600E MAP2K1 C121S melanoma decreased response Selumetinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E mutation and overexpressing MAP2K1 C121S were less sensitive than those overexpressing wild-type MAP2K1 to Selumetinib (AZD6244)-induced inhibition of Mapk pathway activation and cell proliferation in culture (PMID: 24448821). 24448821
BRAF V600E MAP2K1 C121S melanoma sensitive VX-11e Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 C121S demonstrated sensitivity to treatment with VX-11e, resulting in decreased cell growth in culture (PMID: 24265153). 24265153
BRAF V600E MAP2K1 C121S melanoma resistant Dabrafenib + Trametinib Preclinical Actionable In a preclinical study, MAP2K1 C121S conferred resistance to the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) in BRAF V600E-mutant melanoma cells in culture (PMID: 24265154). 24265154
BRAF V600E MAP2K1 C121S melanoma resistant Vemurafenib Case Reports/Case Series Actionable In a clinical case study, a patient harboring BRAF V600E demonstrated an initial response to treatment with Zelboraf (vemurafenib), but progressed following emergence of a MAP2K1 C121S mutation (PMID: 21383288). 21383288
BRAF V600E MAP2K1 C121S melanoma resistant PLX4720 Preclinical Actionable In a preclinical study, expression of MAP2K1 C121S conferred resistance to PLX4720 in melanoma cells harboring BRAF V600E in culture (PMID: 21383288). 21383288
BRAF V600E MAP2K1 C121S melanoma conflicting Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 C121S demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 C121S melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 C121S was resistant to Zelboraf (vemurafenib) in culture (PMID: 28986383). 28986383
BRAF V600E MAP2K1 C121S melanoma conflicting Trametinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 C121S was resistant to Mekinist (trametinib) in culture (PMID: 28986383). 28986383
BRAF V600E MAP2K1 C121S melanoma conflicting Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 C121S in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 C121S melanoma sensitive Binimetinib Preclinical - Cell culture Actionable In a preclinical study, Mektovi (binimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 C121S in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 C121S melanoma sensitive Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, Tafinlar (dabrafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 C121S in culture (PMID: 36442478). 36442478
MAP2K1 C121S MAP2K1 P124R melanoma predicted - sensitive Trametinib Case Reports/Case Series Actionable In a clinical case study, Mekinist (trametinib) resulted in a partial response after two months of treatment in a patient with melanoma harboring MAP2K1 C121S and MAP2K1 P124R (PMID: 36901951). 36901951
BRAF V600E MAP2K1 C121S melanoma sensitive Encorafenib Preclinical - Cell culture Actionable In a preclinical study, Braftovi (encorafenib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 C121S in culture (PMID: 36442478). 36442478