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| Profile Name | MAP2K1 mutant |
| Gene Variant Detail | |
| Relevant Treatment Approaches |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| MAP2K1 F53S | Advanced Solid Tumor | sensitive | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, CI-1040 (PD184352) inhibited kinase activity of MAP2K1 F53S in an in vitro assay and decreased Erk phosphorylation in cells expressing MAP2K1 F53S in culture (PMID: 12370306). | 12370306 | |
| BRAF V600E MAP2K1 F53S | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53S in culture (PMID: 28986383). | 28986383 | |
| BRAF V600E MAP2K1 F53S | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53S was resistant to Zelboraf (vemurafenib) in culture (PMID: 28986383). | 28986383 | |
| MAP2K1 K57_G61del | lymphatic system cancer | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a pediatric patient with Langerhans cell histiocytosis harboring MAP2K1 K57_G61del treated with Mekinist (trametinib) achieved a rapid complete response and had no active disease over 22 months of treatment (PMID: 32991018). | 32991018 | |
| MAP2K1 V60E | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, a melanoma cell line expressing MAP2K1 V60E demonstrated resistance to Tafinlar (dabrafenib) in culture (PMID: 24265153). | 24265153 | |
| MAP2K1 V60E | melanoma | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, a melanoma cell line expressing MAP2K1 V60E demonstrated resistance to Mekinist (trametinib) in culture (PMID: 24265153). | 24265153 | |
| BRAF V600E MAP2K1 V60E | melanoma | sensitive | VX-11e | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 V60E demonstrated sensitivity to treatment with VX-11e, resulting in decreased cell growth in culture (PMID: 24265153). | 24265153 | |
| BRAF V600E MAP2K1 V60E | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 V60E demonstrated resistance to treatment with Tafinlar (dabrafenib) in culture, resulting in sustained Map2k1/2 and Erk1/2 phosphorylation (PMID: 24265153). | 24265153 | |
| BRAF V600X MAP2K1 V60E NRAS T58I NRAS Q61R | melanoma | predicted - resistant | Vemurafenib | Clinical Study - Cohort | Actionable | In a clinical study, a melanoma patient harboring a BRAF V600 mutation developed resistance-associated mutations, MAP2K1 V60E, NRAS T58I, and NRAS Q61R, after 18 weeks of treatment with Zelboraf (vemurafenib) (PMID: 24265153). | 24265153 | |
| MAP2K1 P124S | colorectal cancer | predicted - resistant | Cetuximab + Irinotecan | Case Reports/Case Series | Actionable | In a clinical case study, a patient with KRAS/NRAS-wild-type colorectal cancer who progressed on treatment with Erbitux (cetuximab) and Camptosar (irinotecan) was found through ctDNA testing to have acquired MAP2K1 P124S, and preclinical analysis of colorectal cancer cells expressing MAP2K1 P124S demonstrated increased Erk phosphorylation upon treatment with Erbitux (cetuximab) in culture (PMID: 33322618). | 33322618 | |
| BRAF V600E MAP2K1 P124S | melanoma | sensitive | VX-11e | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124S demonstrated sensitivity to treatment with VX-11e, resulting in decreased cell growth in culture (PMID: 24265153). | 24265153 | |
| BRAF V600E MAP2K1 P124S | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124S demonstrated resistance to treatment with Tafinlar (dabrafenib) in culture (PMID: 24265153). | 24265153 | |
| BRAF V600E MAP2K1 P124S | melanoma | decreased response | Selumetinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, patient-derived melanoma cells harboring BRAF V600E and MAP2K1 P124S demonstrated decreased sensitivity to Selumetinib (AZD6244) compared to cells harboring BRAF V600E alone in culture (PMID: 22197931). | 22197931 | |
| BRAF V600E MAP2K1 P124S | melanoma | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124S demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 24265153). | 24265153 | |
| BRAF V600K MAP2K1 P124S | melanoma | predicted - resistant | Dabrafenib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) treatment resulted in disease progression within 5 weeks in a metastatic melanoma patient harboring BRAF V600K and MAP2K1 P124S (PMID: 24265153). | 24265153 | |
| MAP2K1 Q56P | stomach cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, a gastric cancer cell line harboring MAP2K1 Q56P demonstrated sensitivity to Mekinist (trametinib), resulting in decreased cell viability (PMID: 26582713). | 26582713 | |
| MAP2K1 Q56P | Advanced Solid Tumor | sensitive | PLX4720 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 Q56P displayed sensitivity to the Braf inhibitor, PLX4720, as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 Q56P | stomach cancer | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Koselugo (selumetinib) inhibited growth of a gastric cancer cell line that requires MAP2K1 Q56P and inhibited phosphorylation of ERK in these cells (PMID: 22327936). | 22327936 | |
| MAP2K1 Q56P | lung adenocarcinoma | sensitive | Refametinib | Preclinical | Actionable | In a preclinical study, a lung adenocarcinoma cell line harboring MAP2K1 Q56P demonstrated sensitivity to Refametinib (BAY86-9766), resulting in decreased cell viability (PMID: 26582713). | 26582713 | |
| MAP2K1 Q56P | lung adenocarcinoma | sensitive | Selumetinib | Preclinical | Actionable | In a preclinical study, a lung adenocarcinoma cell line harboring MAP2K1 Q56P demonstrated sensitivity to Selumetinib (AZD6244), resulting in decreased cell viability (PMID: 26582713). | 26582713 | |
| MAP2K1 Q56P | Advanced Solid Tumor | resistant | AZD8330 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 Q56P displayed resistance to the Mek inhibitor, AZD8330, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 Q56P | Erdheim-Chester disease | predicted - sensitive | Cobimetinib | Case Reports/Case Series | Actionable | In a Phase II trial, treatment with Cotellic (cobimetinib) in patients with histiocytic neoplasms resulted in a PET overall response rate of 89% (16/18), with complete response in 72% (13/18) and partial response in 17% (3/18), and stable disease in 6% (1/18) of patients, including a complete response in a patient with Erdheim-Chester disease harboring MAP2K1 Q56P (PMID: 30867592; NCT01953926). | 30867592 | |
| MAP2K1 Q56P | Erdheim-Chester disease | predicted - sensitive | Cobimetinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with refractory Erdheim-Chester disease harboring a MAP2K1 Q56P mutation had a reduction of lymphatic infiltrates to background within a month of receiving Cotellic (cobimetinib) therapy (PMID: 26566875). | 26566875 | |
| MAP2K1 Q56P | Advanced Solid Tumor | resistant | GDC0879 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 Q56P displayed resistance to the Braf inhibitor, GDC-0879, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 Q56P | Advanced Solid Tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 Q56P displayed resistance to Stivarga (regorafenib; BAY 73-4506), as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 Q56P | lung adenocarcinoma | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, a lung adenocarcinoma cell line harboring MAP2K1 Q56P demonstrated sensitivity to Mekinist (trametinib), resulting in decreased cell viability (PMID: 26582713). | 26582713 | |
| MAP2K1 Q56P | lung cancer | predicted - sensitive | LY3214996 | Preclinical - Cell culture | Actionable | In a preclinical study, a lung cancer cell line harboring MAP2K1 Q56P was sensitive to treatment with LY3214996 in culture, demonstrating decreased cell proliferation (PMID: 31744895). | 31744895 | |
| MAP2K1 Q56P | Advanced Solid Tumor | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Koselugo (selumetinib) inhibited colony formation of transformed cells expressing MAP2K1 Q56P in culture (PMID: 25351745). | 25351745 | |
| MAP2K1 Q56P | Advanced Solid Tumor | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 Q56P displayed sensitivity to the Mek inhibitor, Selumetinib (AZD6244), as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 Q56P | Advanced Solid Tumor | resistant | PD98059 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 Q56P displayed resistance to the Mek inhibitor, PD98059, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 Q56P | lung adenocarcinoma | sensitive | PD-0325901 | Preclinical | Actionable | In a preclinical study, a lung adenocarcinoma cell line harboring MAP2K1 Q56P demonstrated sensitivity to PD-0325901, resulting in decreased cell viability (PMID: 26582713). | 26582713 | |
| BRAF V600E MAP2K1 Q56P | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, the combination of Talfinlar (dabrafenib) and Mekinist (trametinib) resulted in improved growth inhibition in melanoma cells harboring BRAF V600E and expressing MAP2K1 Q56P in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 Q56P | melanoma | resistant | PLX4720 | Preclinical | Actionable | In a preclinical study, expression of MAP2K1 Q56P in melanoma cells harboring BRAF V600E conferred resistance to PLX4720 treatment in culture (PMID: 19915144). | 19915144 | |
| BRAF V600E MAP2K1 Q56P | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E expressing MAP2K1 Q56P were resistant to Tafinlar (dabrafenib) mediated growth inhibition and retained MEK and ERK signaling in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 Q56P | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 Q56P demonstrated resistance to treatment with Zelboraf (vemurafenib) in culture (PMID: 28655712). | 28655712 | |
| BRAF V600E MAP2K1 Q56P | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 Q56P was resistant to Zelboraf (vemurafenib) in culture (PMID: 28986383). | 28986383 | |
| BRAF V600E MAP2K1 Q56P | melanoma | conflicting | Trametinib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E expressing MAP2K1 Q56P displayed reduced sensitivity to Mekinist (trametinib) mediated growth inhibition and retained MEK and ERK signaling (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 Q56P | melanoma | conflicting | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 Q56P in culture (PMID: 28986383). | 28986383 | |
| BRAF V600E MAP2K1 Q56P | melanoma | sensitive | Ulixertinib | Preclinical - Cell culture | Actionable | In a preclinical study, BVD-523 (ulixertinib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 Q56P in culture (PMID: 28655712). | 28655712 | |
| BRAF V600E MAP2K1 Q56P | melanoma | resistant | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 Q56P in melanoma cells harboring BRAF V600E conferred resistance to Koselugo (selumetinib) treatment in culture (PMID: 19915144). | 19915144 | |
| BRAF V600E MAP2K1 Q56P NRAS Q61R | melanoma | sensitive | AZD0364 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AZD0364 (ATG-017) decreased phosphorylation of Erk target genes and increased expression of apoptosis markers in melanoma cells harboring BRAF V600E, MAP2K1 Q56P, and NRAS Q61R in culture, and inhibited tumor growth in cell line xenograft models (PMID: 33273059). | 33273059 | |
| MAP2K1 Q56P MAP2K1 H119Y MAP2K1 D351G | colorectal cancer | predicted - sensitive | LY3214996 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, LY3214996 treatment in a colorectal cancer cell line harboring MAP2K1 Q56P, MAP2K1 H119Y, and MAP2K1 D351G led to decreased cell proliferation in culture, and inhibition of tumor growth in a cell line xenograft model (PMID: 31744895). | 31744895 | |
| BRAF V600E MAP2K1 H119P | melanoma | resistant | CI-1040 | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 H119P in melanoma cells harboring BRAF V600E conferred resistance to CI-1040 (PD184352) treatment in culture (PMID: 19915144). | 19915144 | |
| BRAF V600E MAP2K1 H119P | melanoma | resistant | Selumetinib | Preclinical | Actionable | In a preclinical study, expression of MAP2K1 H119P in melanoma cells harboring BRAF V600E conferred resistance to Koselugo (selumetinib) treatment in culture (PMID: 19915144). | 19915144 | |
| MAP2K1 F53C | lymphoma | predicted - resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 F53C in a lymphoma cell line conferred resistance to inhibition of Erk phosphorylation by Zelboraf (vemurafenib) in culture (PMID: 30341394). | 30341394 | |
| MAP2K1 K57E | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, MAP2K1 (MEK1) K57E mutations restored extracellular signal-regulated kinase (ERK) activation in the presence of Tafinlar (dabrafenib) in cultured melanoma cell lines (PMID: 24463458). | 24463458 | |
| BRAF V600E MAP2K1 K57E | melanoma | resistant | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 K57E in a melanoma cell line harboring BRAF V600E conferred resistance to Tafinlar (dabrafenib) in culture (PMID: 25370473). | 25370473 | |
| BRAF V600E MAP2K1 P264L | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P264L in culture (PMID: 28986383). | 28986383 | |
| BRAF V600E MAP2K1 P264L | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P264L was resistant to Zelboraf (vemurafenib) in culture (PMID: 28986383). | 28986383 | |
| BRAF V600E MAP2K1 K59del | melanoma | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del were resistant to growth inhibition by Mekinist (trametinib) in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 K59del | melanoma | sensitive | GSK2126458 + Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del in culture, compared to either agent alone (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 K59del | melanoma | decreased response | GSK2126458 | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 K59del | melanoma | sensitive | Dabrafenib + GSK2126458 | Preclinical | Actionable | In a preclinical study, Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del in culture, compared to either agent alone (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 K59del | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, Talfinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E harboring MAP2K1 K59del in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 K59del | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del were resistant to Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 K59del | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 I99M | melanoma | sensitive | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 I99M demonstrated sensitivity to Tafinlar (dabrafenib) treatment similar to cells expressing wild-type MAP2K1 in culture (PMID: 31925410). | 31925410 | |
| BRAF V600E MAP2K1 I99M | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 I99M demonstrated sensitivity to Mekinist (trametinib) treatment similar to cells expressing wild-type MAP2K1 in culture (PMID: 31925410). | 31925410 | |
| MAP2K1 I111A | Advanced Solid Tumor | decreased response | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, MAP2K1 I111A demonstrated decreased sensitivity to CI-1040 (PD184352) in an in vitro kinase assay (PMID: 12370306). | 12370306 | |
| BRAF V600E MAP2K1 P162S | melanoma | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of BRAF V600E-mutant melanoma cells expressing MAP2K2 P162S in culture (PMID: 24265154). | 24265154 | |
| BRAF V600E MAP2K1 P162S | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) inhibited growth of BRAF V600E-mutant melanoma cells expressing MAP2K2 P162S in culture (PMID: 24265154). | 24265154 | |
| BRAF V600E MAP2K1 P162S | melanoma | sensitive | Dabrafenib | Preclinical | Actionable | In a preclinical study, Tafinlar (dabrafenib) inhibited growth of BRAF V600E-mutant melanoma cells expressing MAP2K2 P162S in culture (PMID: 24265154). | 24265154 | |
| MAP2K1 K57N | colorectal cancer | resistant | Panitumumab | Preclinical | Actionable | In a preclinical study, colorectal cancer cell lines expressing MAP2K1 K57N were insensitive to Vectibix (panitumumab) in culture (PMID: 26644315). | 26644315 | |
| MAP2K1 K57N | Advanced Solid Tumor | sensitive | PLX4720 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 K57N displayed sensitivity to the Braf inhibitor, PLX4720, as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 K57N | Advanced Solid Tumor | resistant | GDC0879 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 K57N displayed resistance to the Braf inhibitor, GDC-0879, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 K57N | Advanced Solid Tumor | resistant | PD98059 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 K57N displayed resistance to the Mek inhibitor, PD98059, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 K57N | Advanced Solid Tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 K57N displayed resistance to Stivarga (regorafenib; BAY 73-4506), as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 K57N | Advanced Solid Tumor | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 K57N displayed sensitivity to the Mek inhibitor, Selumetinib (AZD6244), as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 K57N | Advanced Solid Tumor | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Koselugo (selumetinib) inhibited colony formation of transformed cells expressing MAP2K1 K57N in culture (PMID: 25351745). | 25351745 | |
| MAP2K1 K57N | lymphatic system cancer | sensitive | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with refractory Erdheim-Chester disease harboring a MAP2K1 K57N mutation had a sustained clinical response to Mekinist (trametinib) for over 6 months (PMID: 26566875). | 26566875 | |
| MAP2K1 K57N | lung adenocarcinoma | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Koselugo (selumetinib) inhibited phosphorylation of ERK in cells expressing MAP2K1 K57N and inhibited MAP2K1 K57N-dependent growth in cell culture (PMID: 18632602). | 18632602 | |
| MAP2K1 K57N | colorectal cancer | sensitive | Panitumumab + Trametinib | Preclinical | Actionable | In a preclinical study, Vectibix (panitumumab) and Mekinist (trametinib) inhibited colorectal cancer cell lines expressing MAP2K1 K57N in culture (PMID: 26644315). | 26644315 | |
| MAP2K1 K57N | colorectal cancer | sensitive | Cetuximab + Trametinib | Preclinical | Actionable | In a preclinical study, Erbitux (cetuximab) and Mekinist (trametinib) inhibited colorectal cancer cell lines expressing MAP2K1 K57N in culture (PMID: 26644315). | 26644315 | |
| MAP2K1 K57N | Advanced Solid Tumor | resistant | AZD8330 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 K57N displayed resistance to the Mek inhibitor, AZD8330, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 K57N | colorectal cancer | resistant | Cetuximab | Preclinical | Actionable | In a preclinical study, colorectal cancer cell lines expressing MAP2K1 K57N were insensitive to Erbitux (cetuximab) in culture (PMID: 26644315). | 26644315 | |
| ALK rearrange MAP2K1 K57N | lung non-small cell carcinoma | sensitive | Ceritinib + Selumetinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, NSCLC patient derived cells harboring an ALK rearrangement demonstrated resistance to Zykadia (ceritinib) due to the acquired mutation MAP2K1 K57N, however, sensitivity was restored to Zykadia (ceritinib) with the addition of Koselugo (selumetinib), resulting in decreased cell survival in culture and reduced tumor volume in xenograft models (PMID: 25394791). | 25394791 | |
| MAP2K1 L118Q | Advanced Solid Tumor | predicted - resistant | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, CI-1040 (PD184352) did not inhibit kinase activity of MAP2K1 L118Q in an in vitro assay (PMID: 12370306). | 12370306 | |
| MAP2K1 L118P | Advanced Solid Tumor | predicted - resistant | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, CI-1040 (PD184352) did not inhibit kinase activity of MAP2K1 L118P in an in vitro assay (PMID: 12370306). | 12370306 | |
| MAP2K1 F129L | Advanced Solid Tumor | resistant | PD98059 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 F129L displayed resistance to the Mek inhibitor, PD98059, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 F129L | Advanced Solid Tumor | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 F129L displayed sensitivity to the Mek inhibitor, Selumetinib (AZD6244), as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 F129L | Advanced Solid Tumor | resistant | GDC0879 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 F129L displayed resistance to the Braf inhibitor, GDC-0879, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 F129L | Advanced Solid Tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 F129L displayed resistance to Stivarga (regorafenib; BAY 73-4506), as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 F129L | Advanced Solid Tumor | sensitive | PLX4720 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 F129L displayed sensitivity to the Braf inhibitor, PLX4720, as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 F129L | colorectal cancer | sensitive | RO4927350 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a colorectal cancer cell line harboring MAP2K1 F129L demonstrated sensitivity to treatment with RO4927350 in culture and in cell line xenograft models, demonstrating inhibition of tumor growth (PMID: 21705440). | 21705440 | |
| MAP2K1 F129L | Advanced Solid Tumor | resistant | AZD8330 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 F129L displayed resistance to the Mek inhibitor, AZD8330, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 P124Q | lymphatic system cancer | predicted - sensitive | Cobimetinib | Case Reports/Case Series | Actionable | In a Phase II trial, treatment with Cotellic (cobimetinib) in patients with histiocytic neoplasms resulted in a PET overall response rate of 89% (16/18), with complete response in 72% (13/18) and partial response in 17% (3/18), and resulted in stable disease in 6% (1/18) of patients, including a complete response in a patient with Erdheim-Chester disease harboring MAP2K1 P124Q (PMID: 30867592; NCT01953926). | 30867592 | |
| BRAF V600K MAP2K1 P124Q | melanoma | sensitive | VX-11e | Preclinical - Cell culture | Actionable | In a preclinical study, VX-11e inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124Q in culture (PMID: 25370473). | 25370473 | |
| BRAF V600K MAP2K1 P124Q | melanoma | decreased response | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600K and MAP2K1 P124Q demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 25370473). | 25370473 | |
| BRAF V600K MAP2K1 P124Q | 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 P124Q in culture (PMID: 25370473). | 25370473 | |
| BRAF V600E MAP2K1 P124Q | melanoma | decreased response | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P124Q demonstrated decreased sensitivity to Tafinlar (dabrafenib) in cell culture (PMID: 25370473). | 25370473 | |
| BRAF V600E MAP2K1 S218D MAP2K1 S222D | melanoma | resistant | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 S218D and S222D in melanoma cells harboring BRAF V600E conferred resistance to Tafinlar (dabrafenib) treatment in culture (PMID: 31925410). | 31925410 | |
| MAP2K1 L98_K104delinsQ | Advanced Solid Tumor | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) treatment failed to inhibit activation of Mek and Erk in human cells expressing MAP2K1 L98_K104delinsQ in culture (PMID: 29768711). | 29768711 | |
| MAP2K1 L98_K104delinsQ | Advanced Solid Tumor | resistant | MK2206 | Preclinical - Cell culture | Actionable | In a preclinical study, MK2206 treatment failed to inhibit activation of Mek and Erk in human cells expressing MAP2K1 L98_K104delinsQ in culture (PMID: 29768711). | 29768711 | |
| MAP2K1 L98_K104delinsQ | Advanced Solid Tumor | resistant | SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, SCH772984 treatment failed to inhibit activation of Mek and Erk in human cells expressing MAP2K1 L98_K104delinsQ in culture (PMID: 29768711). | 29768711 | |
| MAP2K1 L98_K104delinsQ | Advanced Solid Tumor | resistant | U0126 | Preclinical - Cell culture | Actionable | In a preclinical study, U0126 treatment failed to inhibit activation of Mek and Erk in human cells expressing MAP2K1 L98_K104delinsQ in culture (PMID: 29768711). | 29768711 | |
| MAP2K1 L98_K104delinsQ | lymphatic system cancer | predicted - resistant | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with Langerhans cell histiocytosis harboring MAP2K1 L98_K104delinsQ demonstrated progressive disease when treated with Mekinist (trametinib) (PMID: 29768711). | 29768711 | |
| MAP2K1 L118G | Advanced Solid Tumor | decreased response | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, MAP2K1 L118G demonstrated decreased sensitivity to CI-1040 (PD184352) in an in vitro kinase assay (PMID: 12370306). | 12370306 | |
| MAP2K1 I111P | Advanced Solid Tumor | predicted - resistant | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, CI-1040 (PD184352) did not inhibit kinase activity of MAP2K1 I111P in an in vitro assay (PMID: 12370306). | 12370306 | |
| MAP2K1 E41_L54del | lung cancer | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited growth of transformed human lung cells expressing MAP2K1 E41_L54del in culture (PMID: 32122926). | 32122926 | |
| MAP2K1 E41_L54del | Advanced Solid Tumor | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Koselugo (selumetinib) inhibited growth of transformed cells expressing MAP2K1 E41_L54del in culture (PMID: 32122926). | 32122926 | |
| MAP2K1 E41_L54del | lung cancer | no benefit | LY3009120 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed human lung cells expressing MAP2K1 E41_L54del were not sensitive to LY3009120 in culture (PMID: 32122926). | 32122926 | |
| MAP2K1 E41_L54del | lung cancer | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Koselugo (selumetinib) inhibited growth of transformed human lung cells expressing MAP2K1 E41_L54del in culture (PMID: 32122926). | 32122926 | |
| MAP2K1 E41_L54del | Advanced Solid Tumor | no benefit | LY3009120 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing MAP2K1 E41_L54del were not sensitive to LY3009120 in culture (PMID: 32122926). | 32122926 | |
| MAP2K1 E41_L54del | lung cancer | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of transformed human lung cells expressing MAP2K1 E41_L54del in culture (PMID: 32122926). | 32122926 | |
| MAP2K1 E41_L54del | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of transformed cells expressing MAP2K1 E41_L54del in culture (PMID: 32122926). | 32122926 | |
| MAP2K1 E41_L54del | Advanced Solid Tumor | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited growth of transformed cells expressing MAP2K1 E41_L54del in culture (PMID: 32122926). | 32122926 | |
| MAP2K1 mutant | Erdheim-Chester disease | sensitive | Cobimetinib | Guideline | Actionable | Cotellic (cobimetinib) is included in guidelines as preferred first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring mutations in the MAPK pathway such as ARAF, NRAS, KRAS, MAP2K1, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN Guidelines). | detail... | |
| MAP2K1 mutant | Erdheim-Chester disease | sensitive | Trametinib | Guideline | Actionable | Mekinist (trametinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring mutations in the MAPK pathway such as ARAF, NRAS, KRAS, MAP2K1, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN Guidelines). | detail... | |
| MAP2K1 Q56_V60del | ovarian serous carcinoma | predicted - sensitive | Selumetinib | Case Reports/Case Series | Actionable | In a Phase II trial, Koselugo (selumetinib) treatment resulted in a complete response that lasted over 5 years with continuous treatment in a patient with serous ovarian cancer harboring MAP2K1 Q56_V60del (PMID: 26324360). | 26324360 | |
| MAP2K1 F53L | Advanced Solid Tumor | sensitive | PLX4720 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 F53L displayed sensitivity to the Braf inhibitor, PLX4720, as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 F53L | colorectal cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, a colorectal cancer cell line harboring MAP2K1 F53L demonstrated sensitivity to Mekinist (trametinib) in culture, resulting in decreased cell viability (PMID: 26582713). | 26582713 | |
| MAP2K1 F53L | Advanced Solid Tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 F53L displayed resistance to Stivarga (regorafenib; BAY 73-4506), as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 F53L | Advanced Solid Tumor | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Koselugo (selumetinib) inhibited colony formation of transformed cells expressing MAP2K1 F53L in culture (PMID: 25351745). | 25351745 | |
| MAP2K1 F53L | Advanced Solid Tumor | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 F53L displayed sensitivity to the Mek inhibitor, Selumetinib (AZD6244), as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 F53L | colorectal cancer | sensitive | Cetuximab + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Erbitux (cetuximab) and Mekinist (trametinib) decreased viability of colorectal cancer cells harboring MAP2K1 F53L in culture (PMID: 28179366). | 28179366 | |
| MAP2K1 F53L | Advanced Solid Tumor | resistant | PD98059 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 F53L displayed resistance to the Mek inhibitor, PD98059, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 F53L | histiocytic sarcoma | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) treatment resulted in resolution of symptoms within 3 days and a durable complete response for over 2 years in a patient with histiocytic sarcoma harboring MAP2K1 F53L (PMID: 29768143). | 29768143 | |
| MAP2K1 F53L | Advanced Solid Tumor | resistant | AZD8330 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 F53L displayed resistance to the Mek inhibitor, AZD8330, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 F53L | Advanced Solid Tumor | resistant | GDC0879 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 F53L displayed resistance to the Braf inhibitor, GDC-0879, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 F53L | colorectal cancer | resistant | Cetuximab | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 F53L conferred resistance to Erbitux (cetuximab) in colorectal cancer cells in culture (PMID: 28179366). | 28179366 | |
| MAP2K1 D67N | Advanced Solid Tumor | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Koselugo (selumetinib) inhibited colony formation of transformed cells expressing MAP2K1 D67N in culture (PMID: 25351745). | 25351745 | |
| BRAF V600E MAP2K1 D67N | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 D67N was resistant to Zelboraf (vemurafenib) in culture (PMID: 28986383). | 28986383 | |
| BRAF V600E MAP2K1 D67N | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 D67N in culture (PMID: 28986383). | 28986383 | |
| MAP2K1 V211D | Advanced Solid Tumor | sensitive | PLX4720 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 V211D displayed sensitivity to the Braf inhibitor, PLX4720, as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 V211D | Advanced Solid Tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 V211D displayed resistance to Stivarga (regorafenib; BAY 73-4506), as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 V211D | Advanced Solid Tumor | predicted - resistant | Binimetinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mektovi (binimetinib) did not inhibit kinase activity of MAP2K1 V211D in an in vitro assay (PMID: 31227518). | 31227518 | |
| MAP2K1 V211D | Advanced Solid Tumor | predicted - resistant | Cobimetinib | Preclinical - Biochemical | Actionable | In a preclinical study, Cotellic (cobimetinib) did not inhibit kinase activity of MAP2K1 V211D in an in vitro assay (PMID: 31227518). | 31227518 | |
| MAP2K1 V211D | Advanced Solid Tumor | resistant | GDC0879 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 V211D displayed resistance to the Braf inhibitor, GDC-0879, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 V211D | Advanced Solid Tumor | resistant | PD98059 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 V211D displayed resistance to the Mek inhibitor, PD98059, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 V211D | Advanced Solid Tumor | resistant | Selumetinib | Preclinical | Actionable | In a preclinical study, Map2k1 V211D displayed resistance to the Mek inhibitor, Selumetinib (AZD6244), as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 V211D | Advanced Solid Tumor | resistant | AZD8330 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 V211D displayed resistance to the Mek inhibitor, AZD8330, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| BRAF V600E MAP2K1 V211D | melanoma | sensitive | Ulixertinib | Preclinical - Cell culture | Actionable | In a preclinical study, BVD-523 (Ulixertinib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 V211D in culture (PMID: 28655712). | 28655712 | |
| BRAF V600E MAP2K1 V211D | colorectal cancer | resistant | SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to SCH772984 in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 V211D | colorectal cancer | resistant | Cetuximab + Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Koselugo (selumetinib) and Erbitux (cetuximab) combination treatment in culture, likely due to the acquired secondary resistant mutation of MAP2K1 V211D (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 V211D | melanoma | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 V211D demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). | 28655712 | |
| BRAF V600E MAP2K1 V211D | melanoma | sensitive | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 V211D in culture (PMID: 28655712). | 28655712 | |
| BRAF V600E MAP2K1 V211D | melanoma | resistant | CI-1040 | Preclinical | Actionable | In a preclinical study, expression of MAP2K1 V211D in melanoma cells harboring BRAF V600E conferred resistance to CI-1040 (PD184352) treatment in culture (PMID: 19915144). | 19915144 | |
| BRAF V600E MAP2K1 V211D | colorectal cancer | resistant | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Tafinlar (dabrafenib) and Mekinist (trametinib) in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 V211D | colorectal cancer | resistant | Cetuximab + Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 V211D | melanoma | resistant | Selumetinib | Preclinical | Actionable | In a preclinical study, expression of MAP2K1 V211D in melanoma cells harboring BRAF V600E conferred resistance to Koselugo (selumetinib) treatment in culture (PMID: 19915144). | 19915144 | |
| BRAF V600E MAP2K1 V211D | colorectal cancer | resistant | Cetuximab + Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) in culture (PMID: 27312529). | 27312529 | |
| BRAF K601E MAP2K1 V211D | colon cancer | predicted - resistant | Binimetinib + Panitumumab | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic colon cancer harboring BRAF K601E developed progressive disease after 6 weeks of Mektovi (binimetinib) and Vectibix (panitumumab) combination treatment, MAP2K1 V211D was identified as a co-occuring mutation in the biopsy from the new metastasis site (PMID: 31227518). | 31227518 | |
| BRAF K601E MAP2K1 V211D | colon cancer | resistant | Binimetinib + Cetuximab | Preclinical - Pdx | Actionable | In a preclinical study, Mektovi (binimetinib) and Erbitux (cetuximab) combination did not inhibit Rsk and Erk phosphorylation, and had no effect on tumor growth in patient-derived xenograft (PDX) models of metastatic colon cancer harboring BRAF K601E and MAP2K1 V211D (PMID: 31227518). | 31227518 | |
| BRAF K601E MAP2K1 V211D | colon cancer | sensitive | MAP855 | Preclinical - Pdx | Actionable | In a preclinical study, MAP955 inhibited Rsk and Erk phosphorylation, and resulted in 30% tumor regression in patient-derived xenograft (PDX) models of metastatic colon cancer harboring BRAF K601E and MAP2K1 V211D (PMID: 31227518). | 31227518 | |
| BRAF K601E MAP2K1 V211D | colon cancer | resistant | Binimetinib | Preclinical - Pdx | Actionable | In a preclinical study, Mektovi (binimetinib) did not inhibit Rsk and Erk phosphorylation, and had no effect on tumor growth in patient-derived xenograft (PDX) models of metastatic colon cancer harboring BRAF K601E and MAP2K1 V211D (PMID: 31227518). | 31227518 | |
| MAP2K1 C121S | Advanced Solid Tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 C121S displayed resistance to Stivarga (regorafenib; BAY 73-4506), as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 C121S | colorectal cancer | resistant | Cetuximab | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 C121S conferred resistance to Erbitux (cetuximab) in colorectal cancer cells in culture (PMID: 28179366). | 28179366 | |
| MAP2K1 C121S | Advanced Solid Tumor | resistant | PD98059 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 C121S displayed resistance to the Mek inhibitor, PD98059, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 C121S | Advanced Solid Tumor | resistant | AZD8330 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 C121S displayed resistance to the Mek inhibitor, AZD8330, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 C121S | Advanced Solid Tumor | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 C121S displayed sensitivity to the Mek inhibitor, Selumetinib (AZD6244), as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 C121S | Advanced Solid Tumor | resistant | GDC0879 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 C121S displayed resistance to the Braf inhibitor, GDC-0879, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 C121S | Advanced Solid Tumor | sensitive | PLX4720 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 C121S displayed sensitivity to the Braf inhibitor, PLX4720, as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 C121S | colorectal cancer | sensitive | Cetuximab + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Erbitux (cetuximab) and Mekinist (trametinib) decreased viability of colorectal cancer cells harboring MAP2K1 C121S in culture (PMID: 28179366). | 28179366 | |
| BRAF V600E MAP2K1 C121S | melanoma | decreased response | Selumetinib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E mutation and overexpressing MAP2K1 C121S were less sensitive than those overexpressing wild-type MAP2K1 to Selumetinib (AZD6244)-induced inhibition of Mapk pathway activation and cell proliferation in culture (PMID: 24448821). | 24448821 | |
| BRAF V600E MAP2K1 C121S | melanoma | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 C121S demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). | 28655712 | |
| BRAF V600E MAP2K1 C121S | melanoma | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 C121S was resistant to Mekinist (trametinib) in culture (PMID: 28986383). | 28986383 | |
| BRAF V600E MAP2K1 C121S | melanoma | resistant | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, MAP2K1 C121S conferred resistance to the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) in BRAF V600E-mutant melanoma cells in culture (PMID: 24265154). | 24265154 | |
| BRAF V600E MAP2K1 C121S | melanoma | sensitive | VX-11e | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 C121S demonstrated sensitivity to treatment with VX-11e, resulting in decreased cell growth in culture (PMID: 24265153). | 24265153 | |
| BRAF V600E MAP2K1 C121S | melanoma | resistant | PLX4720 | Preclinical | Actionable | In a preclinical study, expression of MAP2K1 C121S conferred resistance to PLX4720 in melanoma cells harboring BRAF V600E in culture (PMID: 21383288). | 21383288 | |
| BRAF V600E MAP2K1 C121S | melanoma | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited Mapk pathway activation and proliferation of melanoma cell line harboring BRAF V600E mutation and overexpressing MAP2K1 C121S in culture (PMID: 24448821). | 24448821 | |
| BRAF V600E MAP2K1 C121S | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 C121S conferred resistance to Zelboraf (vemurafenib) in melanoma cell lines harboring BRAF V600, resulting in decreased sensitivity to Zelboraf (vemurafenib)-induced inhibition of MAPK pathway activation and cell proliferation in culture (PMID: 24448821). | 24448821 | |
| BRAF V600E MAP2K1 C121S | melanoma | resistant | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a patient harboring BRAF V600E demonstrated an initial response to treatment with Zelboraf (vemurafenib), but progressed following emergence of a MAP2K1 C121S mutation (PMID: 21383288). | 21383288 | |
| BRAF V600E MAP2K1 C121S | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 C121S was resistant to Zelboraf (vemurafenib) in culture (PMID: 28986383). | 28986383 | |
| MAP2K1 I111R | Advanced Solid Tumor | predicted - resistant | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, CI-1040 (PD184352) did not inhibit kinase activity of MAP2K1 I111R in an in vitro assay (PMID: 12370306). | 12370306 | |
| MAP2K1 L115A | Advanced Solid Tumor | decreased response | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, MAP2K1 L115A demonstrated decreased sensitivity to CI-1040 (PD184352) in an in vitro kinase assay (PMID: 12370306). | 12370306 | |
| BRAF V600E MAP2K1 I99T | melanoma | resistant | CI-1040 | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 I99T in melanoma cells harboring BRAF V600E conferred resistance to CI-1040 (PD184352) treatment in culture (PMID: 19915144). | 19915144 | |
| BRAF V600E MAP2K1 I99T | melanoma | resistant | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 I99T in melanoma cells harboring BRAF V600E conferred resistance to Koselugo (selumetinib) treatment in culture (PMID: 19915144). | 19915144 | |
| BRAF V600E MAP2K1 I99T | melanoma | resistant | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 I99T demonstrated resistance to Tafinlar (dabrafenib) treatment in culture (PMID: 31925410). | 31925410 | |
| BRAF V600E MAP2K1 I99T | melanoma | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 I99T demonstrated resistance to Mekinist (trametinib) treatment in culture (PMID: 31925410). | 31925410 | |
| BRAF V600E MAP2K1 G128V | melanoma | sensitive | VX-11e | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 G128V demonstrated sensitivity to treatment with VX-11e, resulting in decreased cell growth in culture (PMID: 24265153). | 24265153 | |
| BRAF V600E MAP2K1 G128V | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 G128V demonstrated resistance to treatment with Tafinlar (dabrafenib) in culture, resulting in sustained Map2k1/2 and Erk1/2 phosphorylation (PMID: 24265153). | 24265153 | |
| BRAF V600E MAP2K1 G128V | melanoma | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 G128V demonstrated resistance to treatment with Mekinist (trametinib) in culture, resulting in sustained Map2k1/2 and Erk1/2 phosphorylation (PMID: 24265153). | 24265153 | |
| BRAF V600E MAP2K1 G128V | melanoma | resistant | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, MAP2K1 G128V conferred resistance to the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) in BRAF V600E-mutant melanoma cells in culture (PMID: 24265154). | 24265154 | |
| MAP2K1 I139G | Advanced Solid Tumor | predicted - resistant | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, CI-1040 (PD184352) did not inhibit kinase activity of MAP2K1 I139G in an in vitro assay (PMID: 12370306). | 12370306 | |
| MAP2K1 I103N | Advanced Solid Tumor | decreased response | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, MAP2K1 I103N demonstrated decreased sensitivity to CI-1040 (PD184352) in an in vitro kinase assay (PMID: 12370306). | 12370306 | |
| BRAF V600E MAP2K1 I103N | melanoma | resistant | CI-1040 | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 I103N in melanoma cells harboring BRAF V600E conferred resistance to CI-1040 (PD184352) treatment in culture (PMID: 19915144). | 19915144 | |
| BRAF V600E MAP2K1 I103N | melanoma | resistant | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 I103N in melanoma cells harboring BRAF V600E conferred resistance to Koselugo (selumetinib) treatment in culture (PMID: 19915144). | 19915144 | |
| BRAF V600E MAP2K1 I103N | melanoma | resistant | PD-0325901 | Preclinical | Actionable | In a preclinical study, over expression of MAPK21 I103N in melanoma cells harboring BRAF V600E resulted in insensitivity to growth inhibition by PD-0325901 in cell culture (PMID: 26267534). | 26267534 | |
| BRAF V600E MAP2K1 I103N | melanoma | sensitive | DEL-22379 | Preclinical - Cell culture | Actionable | In a preclinical study, DEL-22379 inhibited growth of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 I103N in culture (PMID: 26267534). | 26267534 | |
| MAP2K1 P124L | lymphatic system cancer | predicted - sensitive | Cobimetinib | Case Reports/Case Series | Actionable | In a Phase II trial, treatment with Cotellic (cobimetinib) in patients with histiocytic neoplasms resulted in a PET overall response rate of 89% (16/18), with complete response in 72% (13/18) and partial response in 17% (3/18), and resulted in stable disease in 6% (1/18) of patients, including a complete response in a patient with mixed histiocytosis harboring MAP2K1 P124L (PMID: 30867592; NCT01953926). | 30867592 | |
| 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 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 | 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 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 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 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 | 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 | 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 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 | 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 | |
| MAP2K1 I139R | Advanced Solid Tumor | decreased response | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, MAP2K1 I139R demonstrated decreased sensitivity to CI-1040 (PD184352) in an in vitro kinase assay (PMID: 12370306). | 12370306 | |
| BRAF V600E MAP2K1 Y134C | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 Y134C in culture (PMID: 28986383). | 28986383 | |
| BRAF V600E MAP2K1 Y134C | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 Y134C was resistant to Zelboraf (vemurafenib) in culture (PMID: 28986383). | 28986383 | |
| MAP2K1 K57T | colorectal cancer | sensitive | Panitumumab + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a combination of Vectibix (panitumumab) and Mekinist (trametinib) caused tumor regression in a patient’s colorectal cancer metastases harboring MAP2K1 K57T after being identified pre-clinically as a combination likely to inhibit MAP2K1 K57T expressing colorectal cancer (PMID: 26644315). | 26644315 | |
| MAP2K1 K57T | colorectal cancer | resistant | Panitumumab | Preclinical | Actionable | In a preclinical study, a colorectal cancer cell line expressing MAP2K1 K57T was resistant to Vectibix (panitumumab) in culture (PMID: 26644315). | 26644315 | |
| MAP2K1 K57T | colorectal cancer | sensitive | Cetuximab + Trametinib | Preclinical | Actionable | In a preclinical study, Erbitux (cetuximab) and Mekinist (trametinib) inhibited colorectal cancer cell lines expressing MAP2K1 K57T in culture (PMID: 26644315). | 26644315 | |
| MAP2K1 K57T | colorectal cancer | predicted - resistant | Cetuximab | Case Reports/Case Series | Actionable | In a clinical case study, a patient with colorectal cancer developed liver metastases harboring MAP2K1 K57T that were insensitive to Erbitux (cetuximab) treatment and the mutation was confirmed to cause resistance in human colorectal cancer cell lines in culture (PMID: 26644315). | 26644315 | |
| 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 | refractory hairy cell leukemia | predicted - sensitive | Cobimetinib + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a single patient with hairy cell leukemia who relapsed after initial response to Zelboraf (vemurafenib) was found to have acquired multiple clones with Mek/Erk activating mutations, of which the MAP2K1 K57T clone became dominant, and demonstrated a sustained response greater than 12 months to combined Zelboraf (vemurafenib) and Cotellic (cobimetinib) treatment (PMID: 30341394). | 30341394 | |
| MAP2K1 I111D | Advanced Solid Tumor | predicted - resistant | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, CI-1040 (PD184352) did not inhibit kinase activity of MAP2K1 I111D in an in vitro assay (PMID: 12370306). | 12370306 | |
| MAP2K1 L115P | Advanced Solid Tumor | resistant | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, CI-1040 (PD184352) did not inhibit kinase activity of MAP2K1 L115P in an in vitro assay and failed to suppress Erk phosphorylation in cells expressing MAP2K1 L115P in culture (PMID: 12370306). | 12370306 | |
| BRAF V600E MAP2K1 L115P | melanoma | resistant | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 L115P in melanoma cells harboring BRAF V600E conferred resistance to Koselugo (selumetinib) treatment in culture (PMID: 19915144). | 19915144 | |
| BRAF V600E MAP2K1 L115P | melanoma | conflicting | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 L115P in culture (PMID: 28986383). | 28986383 | |
| BRAF V600E MAP2K1 L115P | melanoma | conflicting | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 L115P demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). | 28655712 | |
| BRAF V600E MAP2K1 L115P | melanoma | resistant | PD-0325901 | Preclinical | Actionable | In a preclinical study, over expression of MAPK21 L115P in melanoma cells harboring BRAF V600E resulted in insensitivity to growth inhibition by PD-0325901 in cell culture (PMID: 26267534). | 26267534 | |
| BRAF V600E MAP2K1 L115P | colorectal cancer | sensitive | Cetuximab + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 L115P | colorectal cancer | sensitive | Alpelisib + Cetuximab + Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818) and Alpelisib (BYL719) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 L115P | colorectal cancer | resistant | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture, likely due to the acquired secondary resistance mutation MAP2K1 L115P (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 L115P | melanoma | sensitive | DEL-22379 | Preclinical - Cell culture | Actionable | In a preclinical study, DEL-22379 inhibited growth of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 L115P in culture (PMID: 26267534). | 26267534 | |
| BRAF V600E MAP2K1 L115P | colorectal cancer | sensitive | Cetuximab + SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 L115P | colorectal cancer | sensitive | SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 L115P | colorectal cancer | sensitive | Cetuximab + Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 L115P | colorectal cancer | sensitive | Cetuximab + Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 L115P | colorectal cancer | sensitive | Cetuximab + Dabrafenib + SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 L115P | melanoma | resistant | CI-1040 | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 L115P in melanoma cells harboring BRAF V600E conferred resistance to CI-1040 (PD184352) treatment in culture (PMID: 19915144). | 19915144 | |
| BRAF V600E MAP2K1 L115P | colorectal cancer | sensitive | Cetuximab + Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Tafinlar (dabrafenib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 L115P | colorectal cancer | sensitive | Dabrafenib + SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Tafinlar (dabrafenib) and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 L115P | melanoma | conflicting | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 L115P in culture (PMID: 28655712). | 28655712 | |
| BRAF V600E MAP2K1 L115P | melanoma | conflicting | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 L115P was resistant to Zelboraf (vemurafenib) in culture (PMID: 28986383). | 28986383 | |
| MAP2K1 I111S | Advanced Solid Tumor | resistant | AZD8330 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 I111S displayed resistance to the Mek inhibitor, AZD8330, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 I111S | Advanced Solid Tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 I111S displayed resistance to Stivarga (regorafenib; BAY 73-4506), as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 I111S | Advanced Solid Tumor | resistant | PD98059 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 I111S displayed resistance to the Mek inhibitor, PD98059, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 I111S | Advanced Solid Tumor | resistant | GDC0879 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 I111S displayed resistance to the Braf inhibitor, GDC-0879, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 I111S | Advanced Solid Tumor | sensitive | PLX4720 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 I111S displayed sensitivity to the Braf inhibitor, PLX4720, as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| MAP2K1 I111S | Advanced Solid Tumor | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 I111S displayed sensitivity to the Mek inhibitor, Selumetinib (AZD6244), as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 | |
| BRAF V600E MAP2K1 L115R | melanoma | resistant | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 L115R in melanoma cells harboring BRAF V600E conferred resistance to Koselugo (selumetinib) treatment in culture (PMID: 19915144). | 19915144 | |
| BRAF V600E MAP2K1 L115R | melanoma | resistant | CI-1040 | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 L115R in melanoma cells harboring BRAF V600E conferred resistance to CI-1040 (PD184352) treatment in culture (PMID: 19915144). | 19915144 | |
| BRAF V600E MAP2K1 L115R | melanoma | resistant | PLX4720 | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 L115R in melanoma cells harboring BRAF V600E conferred resistance to PLX4720 treatment in culture (PMID: 19915144). | 19915144 | |
| BRAF V600E MAP2K1 P387S NRAS A146T | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were resistant to Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS A146T | melanoma | decreased response | GSK2126458 | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS A146T | melanoma | no benefit | Dabrafenib + GSK2126458 | Preclinical | Actionable | In a preclinical study, Talfinlar (dabrafenib) in combination with Omipalisib (GSK2126458) did not improve the response to human melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS A146T | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS A146T | melanoma | decreased response | Trametinib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were >20-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E and also had reduced sensitivity in comparison to cell lines harboring BRAF V600E and NRAS A146T in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS A146T | melanoma | sensitive | GSK2126458 + Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | decreased response | Trametinib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were >20-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | decreased response | GSK2126458 | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | sensitive | GSK2126458 + Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E, NRAS Q61K, and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were resistant to growth inhibition by Zelboraf (vemurafenib) in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were resistant to Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | conflicting | Dabrafenib + GSK2126458 | Preclinical | Actionable | In a preclinical study, the response of human melanoma cell lines harboring BRAF V600E, NRAS Q61K, and MAP2K1 P387S to Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) was conflicting as one cell line with this mutation profile responded to the combination and another cell line with the mutation profile did not (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T | melanoma | decreased response | GSK2126458 | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T | melanoma | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S were resistant to growth inhibition by Mekinist (trametinib) in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S were resistant Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T | melanoma | sensitive | GSK2126458 + Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, A146T and MAP2K1 P387S were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 I99G | melanoma | resistant | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 I99G demonstrated resistance to Tafinlar (dabrafenib) treatment in culture (PMID: 31925410). | 31925410 | |
| BRAF V600E MAP2K1 I99G | melanoma | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 I99G demonstrated resistance to Mekinist (trametinib) treatment in culture (PMID: 31925410). | 31925410 | |
| MAP2K1 L118D | Advanced Solid Tumor | predicted - resistant | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, CI-1040 (PD184352) did not inhibit kinase activity of MAP2K1 L118D in an in vitro assay (PMID: 12370306). | 12370306 | |
| BRAF V600E MAP2K1 I111N | melanoma | resistant | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 I111N in melanoma cells harboring BRAF V600E conferred resistance to Koselugo (selumetinib) treatment in culture (PMID: 19915144). | 19915144 | |
| BRAF V600E MAP2K1 I111N | melanoma | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 I111N demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). | 28655712 | |
| BRAF V600E MAP2K1 I111N | melanoma | resistant | CI-1040 | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 I111N in melanoma cells harboring BRAF V600E conferred resistance to CI-1040 (PD184352) treatment in culture (PMID: 19915144). | 19915144 | |
| BRAF V600E MAP2K1 I111N | melanoma | sensitive | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 I111N in culture (PMID: 28655712). | 28655712 | |
| MAP2K1 I139N | Advanced Solid Tumor | decreased response | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, MAP2K1 I139N demonstrated decreased sensitivity to CI-1040 (PD184352) in an in vitro kinase assay (PMID: 12370306). | 12370306 | |
| BRAF V600E MAP2K1 E203K | melanoma | conflicting | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 E203K in culture (PMID: 28986383). | 28986383 | |
| BRAF V600E MAP2K1 E203K | melanoma | conflicting | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 E203K demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). | 28655712 | |
| BRAF V600E MAP2K1 E203K | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 E203K demonstrated resistance to treatment with Zelboraf (vemurafenib) in culture (PMID: 28655712). | 28655712 | |
| BRAF V600E MAP2K1 E203K | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 E203K was resistant to Zelboraf (vemurafenib) in culture (PMID: 28986383). | 28986383 | |
| BRAF V600E MAP2K1 E203K | melanoma | sensitive | Ulixertinib | Preclinical - Cell culture | Actionable | In a preclinical study, BVD-523 (ulixertinib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 E203K in culture (PMID: 28655712). | 28655712 | |
| MAP2K1 E203K PIK3CA amp | skin squamous cell carcinoma | predicted - sensitive | Metformin + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a combination of Glucophage (metformin) and Mekinist (trametinib) resulted in a complete clinical response and continued remission for over two years in a patient with cutaneous squamous cell carcinoma with amplification of PIK3CA and harboring MAP2K1 E203K (PMID: 35005996). | 35005996 | |
| MAP2K1 P105_I107del | lymphatic system cancer | predicted - sensitive | Cobimetinib | Case Reports/Case Series | Actionable | In a Phase II trial, treatment with Cotellic (cobimetinib) in patients with histiocytic neoplasms resulted in a PET overall response rate of 89% (16/18), with complete response in 72% (13/18) and partial response in 17% (3/18), and resulted in stable disease in 6% (1/18) of patients, including a complete response in a patient with Erdheim-Chester disease harboring MAP2K1 P105_I107del (PMID: 30867592; NCT01953926). | 30867592 |
| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| NCT04145297 | Phase I | Hydroxychloroquine + Ulixertinib | Ulixertinib (BVD-523) and Hydroxychloroquine in Patients w Advanced MAPK-Mutated Gastrointestinal Adenocarcinomas (UTAH) | Recruiting | USA | 0 |
| NCT04488003 | Phase II | Ulixertinib | Study of Ulixertinib for Patients With Advanced Malignancies Harboring MEK or Atypical BRAF Alterations | Recruiting | USA | 0 |
| NCT01885195 | Phase II | Binimetinib | MEK162 for Patients With RAS/RAF/MEK Activated Tumors | Completed | USA | 0 |
| NCT03087071 | Phase II | Panitumumab Panitumumab + Trametinib | Panitumumab With or Without Trametinib in Treating Patients With Stage IV Colorectal Cancer | Unknown status | USA | 0 |
| NCT04252339 | Phase I | RLY-1971 | RLY-1971 in Subjects With Advanced or Metastatic Solid Tumors | Active, not recruiting | USA | 0 |
| NCT02747537 | Phase II | Irinotecan + Sorafenib | Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors With Sorafenib in Combination With Irinotecan | Withdrawn | 0 | |
| NCT02607813 | Phase I | LXH 254 + Spartalizumab LXH 254 | Phase I Study of LXH254 in Patients With Advanced Solid Tumors Haboring MAPK Pathway Alterations | Completed | USA | ITA | FRA | ESP | DEU | CAN | 4 |
| NCT04566393 | Expanded access | Ulixertinib | Expanded Access to Ulixertinib (BVD-523) in Patients With Advanced MAPK Pathway-Altered Malignancies | Available | USA | 0 |
| NCT01781429 | Phase Ib/II | Ulixertinib | Phase I Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of BVD-523 in Patients With Advanced Malignancies | Completed | USA | 0 |
| NCT03698994 | Phase II | Ulixertinib | Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial) | Active, not recruiting | USA | 1 |