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Molecular Profile Detail

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Profile Name MAP2K1 P124L
Gene Variant Detail

MAP2K1 P124L (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 P124L melanoma sensitive PLX4720 + Selumetinib Preclinical Actionable In a preclinical study, combined treatment with Koselugo (selumetinib) and PLX4720 inhibited growth of melanoma cells harboring BRAF V600E and expressing MAP2K1 P124L in culture (PMID: 19915144). 19915144
BRAF V600E MAP2K1 P124L melanoma resistant Selumetinib Preclinical Actionable In a preclinical study, expression of MAP2K1 P124L in melanoma cells harboring BRAF V600E conferred resistance to Koselugo (selumetinib) in culture (PMID: 19915144). 19915144
BRAF V600K MAP2K1 P124L melanoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600K and MAP2K1 P124L demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 25370473). 25370473
BRAF V600K MAP2K1 P124L melanoma sensitive VX-11e Preclinical Actionable In a preclinical study, VX-11e inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124L in culture (PMID: 25370473). 25370473
BRAF V600K MAP2K1 P124L melanoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124L in culture (PMID: 25370473). 25370473
BRAF V600E MAP2K1 P124L melanoma decreased response Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124L demonstrated a decreased response to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 P124L melanoma predicted - resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124L demonstrated a decreased response to treatment with Zelboraf (vemurafenib) in culture (PMID: 28655712). 28655712
BRAF V600K MAP2K1 P124L melanoma predicted - resistant Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in disease progression within one month in a metastatic melanoma patient harboring BRAF V600K and MAP2K1 P124L (PMID: 31980996). 31980996
BRAF V600E MAP2K1 P124L melanoma resistant PLX4720 Preclinical - Cell culture Actionable In a preclinical study, expression of MAP2K1 P124L in melanoma cells harboring BRAF V600E conferred resistance to PLX4720 treatment in culture (PMID: 19915144). 19915144
BRAF V600E MAP2K1 P124L melanoma predicted - resistant Vemurafenib Case Reports/Case Series Actionable In a clinical case study, Zelboraf (vemurafenib) treatment resulted in disease progression within 6 weeks in a metastatic melanoma patient harboring BRAF V600E and MAP2K1 P124L (PMID: 24265153). 24265153
BRAF V600E MAP2K1 P124L melanoma sensitive Cobimetinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P124L in culture (PMID: 36442478). 36442478