Mitogen-Activated Protein Kinase Kinase Inhibitor

BRAF K483M1
Mitogen-Activated Protein Kinase Kinase Inhibitor + SorafenibSubstitutes	Cutaneous MelanomaALIAS	Predictive	E	Supports Sensitivity Response	3	accepted	EID1457 Preclinical study in melanoma cell lines. Inactivity of BRAF as mediated by specific mutation (D594A, D594V or K483M) or selective pharmacological inhibition leads to MEK hyperactivation through CRAF … (full text at CIViC) PMID 20141835 · Heidorn et al., 2010 · Open in CIViC	civic

BRAF K483M1

Mitogen-Activated Protein Kinase Kinase Inhibitor + SorafenibSubstitutes

Cutaneous MelanomaALIAS

Predictive

Supports Sensitivity Response

accepted

EID1457

Preclinical study in melanoma cell lines. Inactivity of BRAF as mediated by specific mutation (D594A, D594V or K483M) or selective pharmacological inhibition leads to MEK hyperactivation through CRAF … (full text at CIViC)

PMID 20141835 · Heidorn et al., 2010 · Open in CIViC

EGFR T790M1
Mitogen-Activated Protein Kinase Kinase Inhibitor + Naquotinib + OsimertinibSequential	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	3	submitted	EID6318 Clinical study confirmed a beneficial effect from the combination therapy of MEK inhibitors and naquotinib. Inhibited cell proliferation in both naquotinib-resistant and osimertinib-resistant cells, … (full text at CIViC) PMID 29386539 · Ninomiya et al., 2018 · Open in CIViC	civic

EGFR T790M1

Mitogen-Activated Protein Kinase Kinase Inhibitor + Naquotinib + OsimertinibSequential

Lung Non-Small Cell CarcinomaCURATED_BROADER

Predictive

Supports Resistance

submitted

EID6318

Clinical study confirmed a beneficial effect from the combination therapy of MEK inhibitors and naquotinib. Inhibited cell proliferation in both naquotinib-resistant and osimertinib-resistant cells, … (full text at CIViC)

PMID 29386539 · Ninomiya et al., 2018 · Open in CIViC

KRAS Activating Mutation1

KRAS Activating Mutation1
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination	Malignant Pancreatic Neoplasm	Predictive	D	Supports Sensitivity Response	1	submitted	EID7184 MAP-ERK kinase (MEK) inhibition in a large PDA cell line panel. Combinations of MEK and EGFR inhibitors induced apoptosis. Combinatorial effect was observed in the epithelial but not mesenchymal subt… (full text at CIViC) PMID 23918833 · Mirzoeva et al., 2013 · Open in CIViC	civic

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination

Malignant Pancreatic Neoplasm

Predictive

Supports Sensitivity Response

submitted

EID7184

MAP-ERK kinase (MEK) inhibition in a large PDA cell line panel. Combinations of MEK and EGFR inhibitors induced apoptosis. Combinatorial effect was observed in the epithelial but not mesenchymal subt… (full text at CIViC)

PMID 23918833 · Mirzoeva et al., 2013 · Open in CIViC

KRAS G121
Mitogen-Activated Protein Kinase Kinase Inhibitor	Malignant Pancreatic Neoplasm	Predictive	D	Supports Resistance	2	submitted	EID7183 Preclinical study shows strong correlation between KRAS mutational subtype and CNV, and sensitivity to MEK inhibition. Cell lines with a KRAS (V12) mutation and KRAS gains or loss (n=7) are ∼10 times … (full text at CIViC) PMID 25167228 · Hamidi et al., 2014 · Open in CIViC	civic

KRAS G121

Malignant Pancreatic Neoplasm

Predictive

Supports Resistance

submitted

EID7183

Preclinical study shows strong correlation between KRAS mutational subtype and CNV, and sensitivity to MEK inhibition. Cell lines with a KRAS (V12) mutation and KRAS gains or loss (n=7) are ∼10 times … (full text at CIViC)

PMID 25167228 · Hamidi et al., 2014 · Open in CIViC

BRAF A598V1
BRAF Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination	Melanoma	Predictive	C	Does Not Support Sensitivity Response	3	accepted	EID7635 In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC	civic

BRAF A598V1

BRAF Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination

Predictive

Does Not Support Sensitivity Response

accepted

EID7635

In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC)

PMID 31580757 · Menzer et al., 2019 · Open in CIViC

BRAF G4691
BRAF Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination	Melanoma	Predictive	B	Supports Sensitivity Response	3	accepted	EID7634 In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC	civic

BRAF G4691

BRAF Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination

Predictive

Supports Sensitivity Response

accepted

EID7634

PMID 31580757 · Menzer et al., 2019 · Open in CIViC

BRAF L5971
BRAF Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination	Melanoma	Predictive	B	Supports Sensitivity Response	3	submitted	EID7632 In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC	civic

BRAF L5971

BRAF Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination

Predictive

Supports Sensitivity Response

submitted

EID7632

PMID 31580757 · Menzer et al., 2019 · Open in CIViC

BRAF V600D1
BRAF Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination	Melanoma	Predictive	C	Supports Sensitivity Response	3	accepted	EID7629 In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC	civic

BRAF V600D1

BRAF Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination

Predictive

Supports Sensitivity Response

accepted

EID7629

PMID 31580757 · Menzer et al., 2019 · Open in CIViC

BRAF V600_K601>E1
BRAF Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination	Melanoma	Predictive	C	Supports Sensitivity Response	3	accepted	EID7630 In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC	civic

BRAF V600_K601>E1

BRAF Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination

Predictive

Supports Sensitivity Response

accepted

EID7630

PMID 31580757 · Menzer et al., 2019 · Open in CIViC

BRAF V600M1
BRAF Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination	Melanoma	Predictive	B	Supports Sensitivity Response	3	submitted	EID7631 In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC	civic

BRAF V600M1

BRAF Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination

Predictive

Supports Sensitivity Response

submitted

EID7631

PMID 31580757 · Menzer et al., 2019 · Open in CIViC

BRAF V600R1
BRAF Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination	Melanoma	Predictive	B	Supports Sensitivity Response	4	submitted	EID7628 In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC	civic

BRAF V600R1

BRAF Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination

Predictive

Supports Sensitivity Response

submitted

EID7628

PMID 31580757 · Menzer et al., 2019 · Open in CIViC

BRAF V601E2
BRAF Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination	Melanoma	Predictive	B	Supports Sensitivity Response	3	submitted	EID7633 In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC	civic
Mitogen-Activated Protein Kinase Kinase Inhibitor	Melanoma	Predictive	C	Does Not Support Sensitivity Response	3	submitted	EID7627 In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC	civic

BRAF V601E2

BRAF Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination

Predictive

Supports Sensitivity Response

submitted

EID7633

PMID 31580757 · Menzer et al., 2019 · Open in CIViC

Predictive

Does Not Support Sensitivity Response

submitted

EID7627

PMID 31580757 · Menzer et al., 2019 · Open in CIViC

CUL1 Fusion1
Mitogen-Activated Protein Kinase Kinase Inhibitor	Ovarian Serous AdenocarcinomaALIAS	Predictive	C	Supports Sensitivity Response	2	accepted	EID1662 One patient with low-grade serous ovarian cancer had an in-frame fusion between the BRAF kinase domain and CUL1 identified by panel sequencing (MSK-IMPACT), with expression confirmed by whole-transcri… (full text at CIViC) PMID 26324360 · Grisham et al., 2015 · Open in CIViC	civic

CUL1 Fusion1

Ovarian Serous AdenocarcinomaALIAS

Predictive

Supports Sensitivity Response

accepted

EID1662

One patient with low-grade serous ovarian cancer had an in-frame fusion between the BRAF kinase domain and CUL1 identified by panel sequencing (MSK-IMPACT), with expression confirmed by whole-transcri… (full text at CIViC)

PMID 26324360 · Grisham et al., 2015 · Open in CIViC

BRAF N486_P490del1
Mitogen-Activated Protein Kinase Kinase Inhibitor	Solid NeoplasmCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	submitted	EID7562 BRAF β3-αC deletions (BRAF N486_P490del, del T488_P492del, or P490_Q494del) are kinase-activating alterations, independent of CRAF and dimerization. Theses BRAF deletions are activating through restr… (full text at CIViC) PMID 26996308 · Foster et al., 2016 · Open in CIViC	civic

BRAF N486_P490del1

Solid NeoplasmCURATED_BROADER

Predictive

Supports Sensitivity Response

submitted

EID7562

BRAF β3-αC deletions (BRAF N486_P490del, del T488_P492del, or P490_Q494del) are kinase-activating alterations, independent of CRAF and dimerization. Theses BRAF deletions are activating through restr… (full text at CIViC)

PMID 26996308 · Foster et al., 2016 · Open in CIViC

MET Overexpression1
C-Met Inhibitor + ERBB3 Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination	Uveal Melanoma	Predictive	D	Supports Sensitivity Response	3	submitted	EID3037 MEK inhibitors improve survival in cutaneous melanoma patients but show only modest efficacy in metastatic uveal melanoma patients. In this study, we screened for growth factors that elicited resistan… (full text at CIViC) PMID 25952648 · Cheng et al., 2015 · Open in CIViC	civic

MET Overexpression1

C-Met Inhibitor + ERBB3 Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination

Uveal Melanoma

Predictive

Supports Sensitivity Response

submitted

EID3037

MEK inhibitors improve survival in cutaneous melanoma patients but show only modest efficacy in metastatic uveal melanoma patients. In this study, we screened for growth factors that elicited resistan… (full text at CIViC)

PMID 25952648 · Cheng et al., 2015 · Open in CIViC