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Profile Name | BRAF N486_P490del |
Gene Variant Detail | |
Relevant Treatment Approaches | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor |
Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|---|
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 | 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 | 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 |
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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 |
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