Reference Detail

Ref Type Journal Article
PMID (27312529)
Authors Oddo D, Sennott EM, Barault L, Valtorta E, Arena S, Cassingena A, Filiciotto G, Marzolla G, Elez E, van Geel RM, Bartolini A, Crisafulli G, Boscaro V, Godfrey JT, Buscarino M, Cancelliere C, Linnebacher M, Corti G, Truini M, Siravegna G, Grasselli J, Gallicchio M, Bernards R, Schellens JH, Tabernero J, Engelman JA, Sartore-Bianchi A, Bardelli A, Siena S, Corcoran RB, Di Nicolantonio F
Title Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer.
Journal Cancer research
Vol 76
Issue 15
Date 2016 Aug 01
URL
Abstract Text Although recent clinical trials of BRAF inhibitor combinations have demonstrated improved efficacy in BRAF-mutant colorectal cancer, emergence of acquired resistance limits clinical benefit. Here, we undertook a comprehensive effort to define mechanisms underlying drug resistance with the goal of guiding development of therapeutic strategies to overcome this limitation. We generated a broad panel of BRAF-mutant resistant cell line models across seven different clinically relevant drug combinations. Combinatorial drug treatments were able to abrogate ERK1/2 phosphorylation in parental-sensitive cells, but not in their resistant counterparts, indicating that resistant cells escaped drug treatments through one or more mechanisms leading to biochemical reactivation of the MAPK signaling pathway. Genotyping of resistant cells identified gene amplification of EGFR, KRAS, and mutant BRAF, as well as acquired mutations in KRAS, EGFR, and MAP2K1 These mechanisms were clinically relevant, as we identified emergence of a KRAS G12C mutation and increase of mutant BRAF V600E allele frequency in the circulating tumor DNA of a patient at relapse from combined treatment with BRAF and MEK inhibitors. To identify therapeutic combinations capable of overcoming drug resistance, we performed a systematic assessment of candidate therapies across the panel of resistant cell lines. Independent of the molecular alteration acquired upon drug pressure, most resistant cells retained sensitivity to vertical MAPK pathway suppression when combinations of ERK, BRAF, and EGFR inhibitors were applied. These therapeutic combinations represent promising strategies for future clinical trials in BRAF-mutant colorectal cancer. Cancer Res; 76(15); 4504-15. ©2016 AACR.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 KRAS A146T KRAS A146V colorectal cancer resistant Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS A146V and A146T mutations and subsequent resistance to Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS A146T KRAS A146V colorectal cancer resistant Cetuximab + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS A146V and A146T mutations and subsequent resistance to Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Tafinlar (dabrafenib) in culture (PMID: 27312529). 27312529
BRAF V600E 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 cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E colorectal cancer no benefit Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cell lines harboring BRAF V600E demonstrated decreased response to Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS amp colorectal cancer resistant Dabrafenib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS amplification and subsequent resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment were resistant to combination therapy consisting of Tafinlar (dabrafenib) and SCH772984 in culture (PMID: 27312529). 27312529
BRAF amp BRAF V600E colorectal cancer resistant Cetuximab + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired BRAF V600E amplification and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS G12D colorectal cancer resistant Cetuximab + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) combination treatment in culture, likely due to the acquisition of KRAS G12D (PMID: 27312529). 27312529
BRAF V600E KRAS G13D colorectal cancer resistant Cetuximab + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Selumetinib (AZD6244) 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 KRAS A146T KRAS A146V colorectal cancer resistant Cetuximab + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS A146V and A146T mutations and subsequent resistance to Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Selumetinib (AZD6244) 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 Selumetinib (AZD6244) and Erbitux (cetuximab) combination treatment in culture, likely due to the acquired secondary resistant mutation of MAP2K1 V211D (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 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 amp BRAF V600E 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 Selumetinib (AZD6244) and Erbitux (cetuximab) combination treatment in culture, likely due to the acquired BRAF V600E amplification (PMID: 27312529). 27312529
BRAF V600E KRAS amp colorectal cancer resistant Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS amplification and subsequent resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS G13D colorectal cancer resistant Dabrafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Tafinlar (dabrafenib) and Mekinist (trametinib) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS G13D colorectal cancer resistant SCH772984 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to SCH772984 in culture (PMID: 27312529). 27312529
BRAF V600E colorectal cancer sensitive Dabrafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Tafinlar (dabrafenib) and Mekinist (trametinib) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E KRAS G13D colorectal cancer resistant Alpelisib + Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS A146T colorectal cancer resistant Cetuximab + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment in culture, likely due to the acquired secondary resistance mutation KRAS A146T (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 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 KRAS amp colorectal cancer resistant Cetuximab + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment in culture, likely due to the acquired KRAS amplification (PMID: 27312529). 27312529
BRAF V600E 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 cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E KRAS amp colorectal cancer resistant SCH772984 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS amplification and subsequent resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment were resistant to SCH772984 in culture (PMID: 27312529). 27312529
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 colorectal cancer sensitive Cetuximab + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) and Erbitux (cetuximab) combination treatment inhibited survival of colorectal cancer cell lines harboring BRAF V600E 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 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 cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E KRAS G12D 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 KRAS G12D mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E 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 cell lines harboring BRAF V600E 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 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 amp BRAF V600E colorectal cancer resistant SCH772984 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired BRAF V600E amplification and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to SCH772984 in culture (PMID: 27312529). 27312529
BRAF V600E colorectal cancer sensitive Cetuximab + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) and Erbitux (cetuximab) combination treatment inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E KRAS A146T KRAS A146V colorectal cancer resistant Alpelisib + Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to combination treatment consisting of Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) in culture, likely due to the acquisition of KRAS A146V and A146T secondary resistance mutations (PMID: 27312529). 27312529
BRAF V600E KRAS G13D colorectal cancer resistant Cetuximab + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
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 KRAS G13D colorectal cancer resistant Cetuximab + Dabrafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) 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 KRAS A146T 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 cell lines harboring BRAF V600E that acquired a KRAS A146T mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E KRAS G12D colorectal cancer resistant Alpelisib + Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G12D mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS A146T colorectal cancer resistant Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment in culture, likely due to the acquired secondary resistance mutation KRAS A146T (PMID: 27312529). 27312529
BRAF V600E KRAS G12D 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 KRAS G12D mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E 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 cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E KRAS A146T colorectal cancer resistant Cetuximab + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS A146T mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS G13D colorectal cancer resistant Cetuximab + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and SCH772984 in culture (PMID: 27312529). 27312529
BRAF V600E KRAS G13D colorectal cancer resistant Cetuximab + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Tafinlar (dabrafenib) in culture (PMID: 27312529). 27312529
BRAF V600E 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 cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E KRAS G13D colorectal cancer resistant Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment in culture, likely due to the acquisition of KRAS G13D (PMID: 27312529). 27312529
BRAF V600E KRAS A146T KRAS A146V colorectal cancer resistant Cetuximab + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS A146V and A146T mutations and subsequent resistance to Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E 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 cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E KRAS amp colorectal cancer resistant Cetuximab + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS amplification and subsequent resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS A146T colorectal cancer resistant Alpelisib + Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS A146T mutation and subsequent resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) 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