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Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS.

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Nature2017PMID 28783719PMC5648058stubpubmedProvenance
Source
PubMed
Retrieved
Sep 8, 2026
Layer
normalized (units and labels harmonized; values unchanged)
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ING-CIVIC-20260908-000001
Published

Abstract

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Linked entities

Linked entities (9)

How each link was made (MeSH, dictionary, registry reference, curation…) and whether it has been validated. Candidate links are not counted in entity statistics.

Validated 9

Curated evidence

Evidence citing this paper (31)

civicProvenance
Source
CIViC — Clinical Interpretation of Variants in Cancer
Dataset
CIViC evidence items
Version
civic-2026-09-08
Retrieved
Sep 8, 2026
Layer
normalized (units and labels harmonized; values unchanged)
Evidence
expert curation
License
CC0 1.0
PMID
28783719
Run
ING-CIVIC-20260908-000001
Open at source
CuratedShowing 1–31 of 31 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.
TherapyCancerTypeLevelDirection · significanceRating (1–5)StatusEvidenceSource
BRAF V600E2
CetuximabColorectal AdenocarcinomaPredictiveDDoes Not Support Sensitivity Response3rejected
EID12446

Cell growth of several BRAF mutant cell lines were analyzed in response to treatment with increasing concentrations of cetuximab (0-300nM). Cell lines with activating BRAF mutations were insensitive, … (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
〃Malignant NeoplasmALIASPredictiveDDoes Not Support Sensitivity Response3submitted
EID12445

Several BRAF mutant cell lines were analyzed in response to treatment with increasing concentrations of cetuximab (0-300nM). Impact on signalling was measured: ERK signalling by western blot and RAS-G… (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
BRAF G466V7
CetuximabLung Non-Small Cell CarcinomaCURATED_BROADERPredictiveDSupports Sensitivity Response3rejected
EID12441

Several BRAF mutant cell lines were analyzed in response to treatment with increasing concentrations of cetuximab (0-300nM). Cell-growth and impact on signalling was measured: ERK signalling by wester… (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
VemurafenibLung Non-Small Cell CarcinomaCURATED_BROADERPredictiveDSupports Resistance3rejected
EID12439

Several BRAF mutant cell lines were treated with vemurafenib, A375 (BRAF V600E) was used as a positive control. Two non-small cell cancer cell lines (H1666 and CAL-12T) containing the BRAF G466V mutat… (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
CetuximabMalignant Colorectal NeoplasmCURATED_BROADERPredictiveDSupports Sensitivity Response3submitted
EID12437

In the study with a tumour from a patient with metastatic colorectal cancer BRAF (G466V) and wild-type RAS and NF1. Treament with Panitumumab and irinotecan cause tumour regression. And in tumour cell… (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
Irinotecan + PanitumumabCombinationMalignant Colorectal NeoplasmCURATED_BROADERPredictiveDSupports Sensitivity Response3accepted
EID7552

In the study with a tumor from a patient with metastatic colorectal cancer BRAF (G466V) and wild-type RAS and NF1. Treament with Panitumumab and irinotecan cause tumor regression. And in tumor cells o… (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
VemurafenibMalignant Colorectal NeoplasmCURATED_BROADERPredictiveDDoes Not Support Sensitivity Response3accepted
EID7553

In the study with a tumor from a patient with metastatic colorectal cancer BRAF (G466V) and wild-type RAS and NF1. Treatment with Panitumumab and irinotecan cause tumor regression. And in tumor cells … (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
TrametinibMalignant NeoplasmALIASPredictiveDSupports Sensitivity Response3submitted
EID12452

Cell lines were treated with varying concentrations of trametinib for 3 days. Viability was measured by ATP-Glo. NSCLC cell lines H1666 and CAL-12T bearing the BRAF G466V mutation were sensitive with… (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
VemurafenibSolid NeoplasmCURATED_BROADERPredictiveDDoes Not Support Sensitivity Response3accepted
EID7554

RAF inhibitor vemurafenib failed to inhibit ERK signaling in tumor cells and NIH3T3 that express class 3 BRAF mutations (G466V, G466E, D594G, D594N, and G596R).

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
BRAF G596R2
CetuximabMalignant Colorectal NeoplasmCURATED_BROADERPredictiveDSupports Sensitivity Response3submitted
EID12443

Several BRAF mutant cell lines were analyzed in response to treatment with increasing concentrations of cetuximab (0-300nM). Cell-growth and impact on signalling was measured: ERK signalling by wester… (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
VemurafenibSolid NeoplasmCURATED_BROADERPredictiveDDoes Not Support Sensitivity Response3submitted
EID7558

RAF inhibitor vemurafenib failed to inhibit ERK signaling in tumor cells and NIH3T3 that express class 3 BRAF mutations (G466V, G466E, D594G, D594N, and G596R).

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
BRAF D594G3
TrametinibMalignant NeoplasmALIASPredictiveDSupports Sensitivity Response2submitted
EID7760

In a BRAF-mutation inducible model in the NIH3T3 cell line, class 3 BRAF mutations (G466V, G466E, D594G, D594N, and G596R) were resistant to vemurafenib but sensitive to MEK-inhibitor trametinib.

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
〃Malignant NeoplasmALIASPredictiveDSupports Sensitivity Response3rejected
EID12453

Cell lines were treated with varying concentrations of trametinib for 3 days. Viability was measured by ATP-Glo. The melanoma cell line, SK-MEL-264 (BRAF D594G), was sensitive with low IC50 values (<5… (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
VemurafenibMalignant NeoplasmALIASPredictiveDDoes Not Support Sensitivity Response3accepted
EID7556

RAF inhibitor vemurafenib failed to inhibit ERK signaling in tumor cells and NIH3T3 that express class 3 BRAF mutations (G466V, G466E, D594G, D594N, and G596R).

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
BRAF D594N2
VemurafenibMalignant NeoplasmALIASPredictiveDDoes Not Support Sensitivity Response3submitted
EID7557

RAF inhibitor vemurafenib failed to inhibit ERK signaling in tumor cells and NIH3T3 that express class 3 BRAF mutations (G466V, G466E, D594G, D594N, and G596R).

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
(functional)—UNRESOLVEDFunctionalDSupports Gain Of Function5submitted
EID12985

BRAF p.Asp594Asn (NM_004333.6:c.1780G>A) causes increased MEK phosphorylation, increased ratio of pERK/ERK, increased signaling through RAF1 (CRAF), it has loss of kinase activity. Class 3 BRAF varian… (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
BRAF D594N + BRAF G466A2
CetuximabMalignant NeoplasmALIASPredictiveDDoes Not Support Sensitivity Response3submitted
EID12448

A patient with a metastatic collecting duct carcinoma of the kidney was treated with combination chemotherapy and responded except for one ovarian lesion. A PDX was generated from the ovarian lesion. … (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
Capmatinib + CrizotinibSubstitutesMalignant NeoplasmALIASPredictiveDSupports Sensitivity Response3submitted
EID12449

A patient with a metastatic collecting duct carcinoma of the kidney was treated with combination chemotherapy and responded except for one ovarian lesion. A PDX was generated from the ovarian lesion. … (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
BRAF delL485_P490insY + BRAF G469A1
CetuximabMalignant NeoplasmALIASPredictiveDDoes Not Support Sensitivity Response3submitted
EID12444

Several BRAF mutant cell lines were analyzed in response to treatment with increasing concentrations of cetuximab (0-300nM). Cell-growth and impact on signalling was measured: ERK signalling by wester… (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
BRAF G466E + HRAS Q61KHRASBRAF2
CetuximabMalignant NeoplasmALIASPredictiveDDoes Not Support Sensitivity Response3submitted
EID12447

Several BRAF mutant cell lines were analyzed in response to treatment with increasing concentrations of cetuximab (0-300nM). Cell-growth and impact on signalling was measured: ERK signalling by wester… (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
TrametinibMalignant NeoplasmALIASPredictiveDSupports Sensitivity Response3submitted
EID12454

Cell lines were treated with varying concentrations of trametinib for 3 days. Viability was measured by ATP-Glo. The melanoma cell line, SK-MEL-208 (BRAF G466E + HRAS Q61K), was sensitive with a low I… (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
KRAS G12S + KRAS Q61K1
TrametinibMalignant NeoplasmALIASPredictiveDSupports Sensitivity Response3submitted
EID12455

Cell lines were treated with varying concentrations of trametinib for 3 days. Viability was measured by ATP-Glo. Lung adenocarcinoma cell lines A549 (KRAS G12S) and CALU-6 (KRAS Q61K) were sensitive w… (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
NRAS Q61K1
TrametinibMalignant NeoplasmALIASPredictiveDSupports Sensitivity Response3submitted
EID12456

Cell lines were treated with varying concentrations of trametinib for 3 days. Viability was measured by ATP-Glo. The lung large cell carcinoma cell line, H1299 (NRAS Q61K), was sensitive with a low IC… (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
BRAF G466V + NRAS Q61KNRASBRAF2
CetuximabMalignant NeoplasmALIASPredictiveDSupports Resistance3submitted
EID12450

Expression of mutant (Q61K) but not wildtype NRAS in the non-small cell lung carcinoma cell line, H1666 (BRAF G466V), resulted in reduced sensitivity to cetuximab as measured by cell growth and RAS-GT… (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
TrametinibMalignant NeoplasmALIASPredictiveDDoes Not Support Resistance3submitted
EID12451

Expression of mutant (Q61K) but not wildtype NRAS in the non-small cell lung carcinoma cell line, H1666 (BRAF G466V), resulted in reduced sensitivity to cetuximab but not trametinib as measured by cel… (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
NRAS Q61R1
VemurafenibMalignant NeoplasmALIASPredictiveDSupports Resistance3submitted
EID12438

Several BRAF mutant cell lines were treated with vemurafenib, A375 (BRAF V600E) was used as a positive control. The SK-MEL-2 cell line (NRAS Q61R) was not inhibited.

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
PDGFRA Amplification1
TrametinibMalignant NeoplasmALIASPredictiveDDoes Not Support Sensitivity Response3submitted
EID12457

Cell lines were treated with varying concentrations of trametinib for 3 days. Viability was measured by ATP-Glo. The lung large cell carcinoma cell line, H661 (PDGFRA amplification), was not sensitive… (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
BRAF G466E1
VemurafenibSolid NeoplasmCURATED_BROADERPredictiveDDoes Not Support Sensitivity Response3submitted
EID7555

RAF inhibitor vemurafenib failed to inhibit ERK signaling in tumor cells and NIH3T3 that express class 3 BRAF mutations (G466V, G466E, D594G, D594N, and G596R).

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
BRAF D594H1
(functional)—UNRESOLVEDFunctionalDSupports Gain Of Function2submitted
EID7652

An in vitro kinase assay showed that BRAF D594H, a class 3 BRAF mutation, lacked kinase activity as measured by presence of phosphorylated MEK1/2. RAS-dependent activation of MEK1/2 and ERK1/2 was see… (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
BRAF G469A1
(functional)—UNRESOLVEDFunctionalDSupports Gain Of Function5submitted
EID12982

BRAF p.Gly469Ala (NM_004333.6:c.1406G>C) causes increased MEK phosphorylation, and increased ratio of pERK/ERK. Class 2 BRAF variant.

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic
BRAF K601E1
(functional)—UNRESOLVEDFunctionalDSupports Gain Of Function4submitted
EID12921

BRAF p.Lys601Glu (NM_004333.6:c.1801A>G) causes increased phosphorylation of substrate of BRAF.

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic