Molecular Profile Detail

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Profile Name BRAF V600E MAP2K1 F53L
Gene Variant Detail

BRAF V600E (gain of function)

MAP2K1 F53L (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 F53L melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53L was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 F53L melanoma conflicting Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited Mek but not Erk phosphorylation and did not inhibit proliferation in a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53L in culture (PMID: 36622773). 36622773
BRAF V600E MAP2K1 F53L melanoma resistant Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, Tafinlar (dabrafenib) inhibited Erk and Mek phosphorylation but did not inhibit proliferation in a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53L in culture (PMID: 36622773). 36622773
BRAF V600E MAP2K1 F53L melanoma sensitive DS03090629 Preclinical - Cell culture Actionable In a preclinical study, DS03090629 inhibited Erk and Mek phosphorylation and proliferation in a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53L in culture (PMID: 36622773). 36622773
BRAF V600E MAP2K1 F53L melanoma resistant Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53L was resistant to Tafinlar (dabrafenib) in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 F53L melanoma resistant Encorafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53L was resistant to Braftovi (encorafenib) in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 F53L 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 F53L in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 F53L 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 F53L in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 F53L melanoma sensitive Cobimetinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) synergistically inhibited viability in a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53L in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 F53L melanoma conflicting Trametinib Preclinical - Biochemical Actionable In a preclinical study, Mekinist (trametinib) inhibited Erk phosphorylation in a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53L in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 F53L colorectal cancer predicted - resistant Binimetinib + Cetuximab + Encorafenib Case Reports/Case Series Actionable In a Phase III (BEACON CRC) trial, two patients with colorectal cancer harboring BRAF V600E demonstrated resistance to treatment with the combination of Braftovi (encorafenib), Mektovi (binimetinib), and Erbitux (cetuximab), and were found to have acquired MAP2K1 F53L in end-of-treatment ctDNA samples (PMID: 39313594; NCT02928224). 39313594