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Profile Name BRAF N486_P490del
Gene Variant Detail

BRAF N486_P490del (gain of function)

Relevant Treatment Approaches MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF N486_P490del ovarian cancer sensitive LY3009120 Preclinical Actionable In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del was sensitive to LY3009120, resulting in inhibition of cell growth and decreased phosphorylation of MEK and ERK in culture (PMID: 26732095). 26732095
BRAF N486_P490del ovarian cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 26732095). 26732095
BRAF N486_P490del ovarian cancer resistant Vemurafenib Preclinical Actionable In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del was resistant to Zelboraf (vemurafenib), resulting in minimal inhibition of both cell growth and phosphorylation of MEK and ERK in culture (PMID: 26732095). 26732095
BRAF N486_P490del ovarian cancer conflicting Dabrafenib Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) resulted in minimal growth inhibitory activity of an ovarian cancer cell line harboring BRAF N486_P490del (PMID: 26732095). 26732095
BRAF N486_P490del pancreatic ductal adenocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a clinical case study, Mekinist (trametinib) treatment resulted in partial response in a patient with pancreatic ductal adenocarcinoma harboring BRAF N486_P490del 8 weeks after initiation of treatment and lasted for 6 months (PMID: 29903880). 29903880
BRAF N486_P490del pancreatic cancer predicted - sensitive Dabrafenib Case Reports/Case Series Actionable In a clinical case study, a patient with pancreatic cancer harboring BRAF N486_P490del had a partial response when treated with Tafinlar (dabrafenib), demonstrating a decrease in both the size of the primary and metastatic lesions and response duration of 6 months (PMID: 31519698). 31519698
BRAF N486_P490del lymphatic system cancer predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a clinical case study, Mekinist (trametinib) treatment in two patients with Langerhans cell histiocytosis harboring BRAF N486_P490del resulted in a complete response with no disease reactivation over 18 months of treatment in one patient and a partial response with stable disease in the lungs maintained over 12 months of treatment in a second patient (PMID: 32991018). 32991018
BRAF N486_P490del pancreatic ductal adenocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Pdx Actionable In a preclinical study, a patient-derived xenograft (PDX) model with pancreatic ductal adenocarcinoma harboring BRAF N486_P490del demonstrated partial inhibition of Erk phosphorylation and moderate inhibition of tumor growth when treated with Mekinist (trametinib) (PMID: 34011980). 34011980
BRAF N486_P490del pancreatic ductal adenocarcinoma predicted - sensitive LY3009120 Preclinical - Pdx & cell culture Actionable In a preclinical study, a patient-derived xenograft (PDX) model with pancreatic ductal adenocarcinoma harboring BRAF N486_P490del demonstrated partial inhibition of Erk phosphorylation and moderate inhibition of tumor growth when treated with LY3009120 (PMID: 34011980). 34011980
BRAF N486_P490del pancreatic ductal adenocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120 + Trametinib Preclinical - Pdx Actionable In a preclinical study, a patient-derived xenograft (PDX) model with pancreatic ductal adenocarcinoma harboring BRAF N486_P490del demonstrated inhibition of Erk phosphorylation and greater inhibition of tumor growth when treated with the combination of Mekinist (trametinib) and LY3009120 compared to either agent alone (PMID: 34011980). 34011980
BRAF N486_P490del melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cobimetinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF N486_P490del demonstrated sensitivity to Cotellic (cobimetinib), resulting in decreased cell viability in culture (PMID: 26996308). 26996308
BRAF N486_P490del ovarian cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cobimetinib Preclinical - Cell culture Actionable In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del demonstrated sensitivity to Cotellic (cobimetinib), resulting in decreased cell viability in culture (PMID: 26996308). 26996308
BRAF N486_P490del melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Mirdametinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF N486_P490del demonstrated sensitivity to Gomekli (mirdametinib), resulting in decreased cell viability in culture (PMID: 26996308). 26996308
BRAF N486_P490del ovarian cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Mirdametinib Preclinical - Cell culture Actionable In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del demonstrated sensitivity to Gomekli (mirdametinib), resulting in decreased cell viability in culture (PMID: 26996308). 26996308
BRAF N486_P490del ovarian cancer predicted - sensitive GDC0879 Preclinical - Cell culture Actionable In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del demonstrated partial sensitivity to GDC0879 in culture (PMID: 26996308). 26996308
BRAF N486_P490del melanoma predicted - sensitive GDC0879 Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF N486_P490del demonstrated partial sensitivity to GDC0879 in culture (PMID: 26996308). 26996308
BRAF N486_P490del melanoma sensitive AZ628 Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF N486_P490del demonstrated sensitivity to AZ628, resulting in decreased cell viability and inhibition of Mek and Erk phosphorylation in culture (PMID: 26996308). 26996308
BRAF N486_P490del ovarian cancer sensitive AZ628 Preclinical - Cell culture Actionable In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del demonstrated sensitivity to AZ628, resulting in decreased cell viability and inhibition of Mek and Erk phosphorylation in culture (PMID: 26996308). 26996308
BRAF N486_P490del melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) failed to reduce phosphorylation of Mek and Erk and did not inhibit viability of a melanoma cell line harboring BRAF N486_P490del in culture (PMID: 26996308). 26996308
BRAF N486_P490del ovarian cancer resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) failed to reduce phosphorylation of Mek and Erk and did not inhibit viability of an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 26996308). 26996308
BRAF N486_P490del pancreatic ductal adenocarcinoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a partial response after 8 weeks of treatment in a patient with metastatic pancreatic ductal adenocarcinoma harboring BRAF N486_P490del (PMID: 36505826). 36505826
BRAF N486_P490del pancreatic ductal adenocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Patient cell culture Actionable In a preclinical study, a pancreatic ductal adenocarcinoma patient-derived organoid model harboring BRAF N486_P490del was sensitive to treatment with Mekinist (trametinib) in culture, demonstrating decreased cell viability (PMID: 37463056). 37463056
BRAF N486_P490del pancreatic ductal adenocarcinoma sensitive Ulixertinib Preclinical - Patient cell culture Actionable In a preclinical study, a pancreatic ductal adenocarcinoma patient-derived organoid model harboring BRAF N486_P490del was sensitive to treatment with Ulixertinib (BVD-523) in culture, demonstrating decreased cell viability (PMID: 37463056). 37463056
BRAF N486_P490del Advanced Solid Tumor predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Biochemical Actionable In a preclinical study, Mekinist (trametinib) inhibited Mek and Erk phosphorylation in cells expressing BRAF N486_P490del in culture (PMID: 37656784). 37656784
BRAF N486_P490del Advanced Solid Tumor predicted - resistant Vemurafenib Preclinical - Biochemical Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit Mek and Erk phosphorylation in cells expressing BRAF N486_P490del in culture (PMID: 37656784). 37656784
BRAF N486_P490del Advanced Solid Tumor predicted - sensitive Dabrafenib Preclinical - Biochemical Actionable In a preclinical study, Tafinlar (dabrafenib) inhibited Mek and Erk phosphorylation in cells expressing BRAF N486_P490del in culture (PMID: 37656784). 37656784
BRAF N486_P490del Advanced Solid Tumor predicted - sensitive LXH 254 Preclinical - Biochemical Actionable In a preclinical study, LXH 254 inhibited Mek and Erk phosphorylation in cells expressing BRAF N486_P490del in culture (PMID: 37656784). 37656784
BRAF N486_P490del ovarian cancer sensitive LXH 254 Preclinical - Cell culture Actionable In a preclinical study, LXH 254 inhibited MAPK signaling and colony formation in an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 37656784). 37656784
BRAF N486_P490del ovarian cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited MAPK signaling and colony formation in an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 37656784). 37656784
BRAF N486_P490del ovarian cancer decreased response Encorafenib Preclinical - Cell culture Actionable In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del was less sensitive to Braftovi (encorafenib) treatment compared to type II RAF inhibitors in culture (PMID: 37656784). 37656784
BRAF N486_P490del ovarian cancer conflicting Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, Tafinlar (dabrafenib) inhibited MAPK signaling and colony formation in an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 37656784). 37656784
BRAF N486_P490del ovarian cancer sensitive Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Nexavar (sorafenib) inhibited colony formation in an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 37656784). 37656784
BRAF N486_P490del ovarian cancer predicted - sensitive Ulixertinib Preclinical - Biochemical Actionable In a preclinical study, Ulixertinib (BVD-523) inhibited metabolic activity in an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 37656784). 37656784
BRAF N486_P490del ovarian cancer predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LXH 254 + Trametinib Preclinical - Biochemical Actionable In a preclinical study, combination of Mekinist (trametinib) and LXH 254 resulted in enhanced inhibition of metabolic activity in an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 37656784). 37656784
BRAF N486_P490del ovarian cancer predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Sorafenib + Trametinib Preclinical - Biochemical Actionable In a preclinical study, combination of Mekinist (trametinib) and Nexavar (sorafenib) resulted in enhanced inhibition of metabolic activity in an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 37656784). 37656784
BRAF N486_P490del pancreatic ductal adenocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib Preclinical - Patient cell culture Actionable In a preclinical study, Mektovi (binimetinib) inhibited growth of organoids derived from pancreatic ductal adenocarcinoma patients harboring BRAF N486_P490del in culture (PMID: 37656784). 37656784
BRAF N486_P490del pancreatic ductal adenocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Patient cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of organoids derived from pancreatic ductal adenocarcinoma patients harboring BRAF N486_P490del in culture (PMID: 37656784). 37656784
BRAF N486_P490del pancreatic ductal adenocarcinoma sensitive SCH772984 Preclinical - Patient cell culture Actionable In a preclinical study, SCH772984 inhibited growth of organoids derived from pancreatic ductal adenocarcinoma patients harboring BRAF N486_P490del in culture (PMID: 37656784). 37656784
BRAF N486_P490del pancreatic ductal adenocarcinoma sensitive Sorafenib Preclinical - Patient cell culture Actionable In a preclinical study, Nexavar (sorafenib) inhibited growth of organoids derived from pancreatic ductal adenocarcinoma patients harboring BRAF N486_P490del in culture (PMID: 37656784). 37656784
BRAF N486_P490del pancreatic ductal adenocarcinoma sensitive LXH 254 Preclinical - Patient cell culture Actionable In a preclinical study, LXH 254 inhibited growth of organoids derived from pancreatic ductal adenocarcinoma patients harboring BRAF N486_P490del in culture (PMID: 37656784). 37656784
BRAF N486_P490del lung adenocarcinoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in complete resolution of the pulmonary lesions and ongoing response after 6 months in a patient with metastatic lung adenocarcinoma harboring BRAF N486_P490del, who remained on treatment at 9 months (PMID: 38479107). 38479107
BRAF N486_P490del pancreatic ductal adenocarcinoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a retrospective analysis, third-line treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a partial response lasting 18 months in a patient with KRAS wild-type, metastatic pancreatic ductal adenocarcinoma harboring BRAF N486_P490del (PMID: 38770091). 38770091