Molecular Profile Detail

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Profile Name BRAF V600E MAP2K1 K57T
Gene Variant Detail

BRAF V600E (gain of function)

MAP2K1 K57T (gain of function)

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 MAP2K1 K57T refractory hairy cell leukemia predicted - sensitive Cobimetinib + Vemurafenib Case Reports/Case Series Actionable In a clinical case study, a patient with hairy cell leukemia harboring BRAF V600E who relapsed after initial response to Zelboraf (vemurafenib) and was found to have acquired multiple clones with Mek/Erk activating mutations, including MAP2K1 K57T, demonstrated a sustained response greater than 12 months to combined Zelboraf (vemurafenib) and Cotellic (cobimetinib) treatment (PMID: 30341394). 30341394
BRAF V600E MAP2K1 K57T hairy cell leukemia predicted - resistant Vemurafenib Case Reports/Case Series Actionable In a clinical case study, a single patient with hairy cell leukemia harboring BRAF V600E, who relapsed after a 38 week remission in response to Zelboraf (vemurafenib) treatment, was found to have acquired multiple clones with Mek/Erk activating mutations, of which the MAP2K1 K57T clone became dominant (PMID: 30341394). 30341394
BRAF V600E MAP2K1 K57T melanoma resistant Cobimetinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57T was resistant to Cotellic (cobimetinib) in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 K57T melanoma resistant Binimetinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57T was resistant to Mektovi (binimetinib) in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 K57T melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57T was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 K57T melanoma resistant Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57T was resistant to Tafinlar (dabrafenib) in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 K57T melanoma resistant Encorafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57T was resistant to Braftovi (encorafenib) in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 K57T 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 K57T in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 K57T melanoma sensitive Dabrafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57T in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 K57T melanoma sensitive Binimetinib + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, the combination of Braftovi (encorafenib) and Mektovi (binimetinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57T in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 K57T colorectal cancer predicted - resistant Cetuximab + Fluorouracil + Leucovorin + Vemurafenib Case Reports/Case Series Actionable In a Phase II trial (MODUL), a patient with metastatic colorectal cancer harboring BRAF V600E was found to have acquired MAP2K1 K57T prior to progression on treatment with the combination of Zelboraf (vemurafenib), Erbitux (cetuximab), Adrucil (fluorouracil), and Wellcovorin (leucovorin) (PMID: 36921494; NCT02291289). 36921494