Publication
Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS.
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- PubMed
- Retrieved
- Sep 8, 2026
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- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CIVIC-20260908-000001
Abstract
Abstract (excerpt)
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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
- cancerMalignant Colorectal Neoplasmcivic_curation1.00
- cancerMalignant Neoplasmcivic_curation1.00
- cancerSolid Neoplasmcivic_curation1.00
- drugIrinotecancivic_curation1.00
- drugPanitumumabcivic_curation1.00
- drugVemurafenibcivic_curation1.00
- geneBRAFcivic_curation1.00
- variantBRAF D594Gcivic_curation1.00
- variantBRAF G466Vcivic_curation1.00
Curated evidence
Evidence citing this paper (31)
- 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
| Therapy | Cancer | Type | Level | Direction · significance | Rating (1–5) | Status | Evidence | Source |
|---|---|---|---|---|---|---|---|---|
| BRAF V600E2 | ||||||||
| Cetuximab | Colorectal Adenocarcinoma | Predictive | D | Does Not Support Sensitivity Response | 3 | rejected | EID12446Cell 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 NeoplasmALIAS | Predictive | D | Does Not Support Sensitivity Response | 3 | submitted | EID12445Several 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 | ||||||||
| Cetuximab | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | rejected | EID12441Several 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 |
| Vemurafenib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | rejected | EID12439Several 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 |
| Cetuximab | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID12437In 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 + PanitumumabCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID7552In 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 |
| Vemurafenib | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Does Not Support Sensitivity Response | 3 | accepted | EID7553In 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 |
| Trametinib | Malignant NeoplasmALIAS | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID12452Cell 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 |
| Vemurafenib | Solid NeoplasmCURATED_BROADER | Predictive | D | Does Not Support Sensitivity Response | 3 | accepted | EID7554RAF 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 | ||||||||
| Cetuximab | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID12443Several 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 |
| Vemurafenib | Solid NeoplasmCURATED_BROADER | Predictive | D | Does Not Support Sensitivity Response | 3 | submitted | EID7558RAF 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 | ||||||||
| Trametinib | Malignant NeoplasmALIAS | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID7760In 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 NeoplasmALIAS | Predictive | D | Supports Sensitivity Response | 3 | rejected | EID12453Cell 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 |
| Vemurafenib | Malignant NeoplasmALIAS | Predictive | D | Does Not Support Sensitivity Response | 3 | accepted | EID7556RAF 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 | ||||||||
| Vemurafenib | Malignant NeoplasmALIAS | Predictive | D | Does Not Support Sensitivity Response | 3 | submitted | EID7557RAF 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) | —UNRESOLVED | Functional | D | Supports Gain Of Function | 5 | submitted | EID12985BRAF 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 | ||||||||
| Cetuximab | Malignant NeoplasmALIAS | Predictive | D | Does Not Support Sensitivity Response | 3 | submitted | EID12448A 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 + CrizotinibSubstitutes | Malignant NeoplasmALIAS | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID12449A 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 | ||||||||
| Cetuximab | Malignant NeoplasmALIAS | Predictive | D | Does Not Support Sensitivity Response | 3 | submitted | EID12444Several 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 | ||||||||
| Cetuximab | Malignant NeoplasmALIAS | Predictive | D | Does Not Support Sensitivity Response | 3 | submitted | EID12447Several 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 |
| Trametinib | Malignant NeoplasmALIAS | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID12454Cell 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 | ||||||||
| Trametinib | Malignant NeoplasmALIAS | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID12455Cell 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 | ||||||||
| Trametinib | Malignant NeoplasmALIAS | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID12456Cell 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 | ||||||||
| Cetuximab | Malignant NeoplasmALIAS | Predictive | D | Supports Resistance | 3 | submitted | EID12450Expression 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 |
| Trametinib | Malignant NeoplasmALIAS | Predictive | D | Does Not Support Resistance | 3 | submitted | EID12451Expression 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 | ||||||||
| Vemurafenib | Malignant NeoplasmALIAS | Predictive | D | Supports Resistance | 3 | submitted | EID12438Several 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 | ||||||||
| Trametinib | Malignant NeoplasmALIAS | Predictive | D | Does Not Support Sensitivity Response | 3 | submitted | EID12457Cell 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 | ||||||||
| Vemurafenib | Solid NeoplasmCURATED_BROADER | Predictive | D | Does Not Support Sensitivity Response | 3 | submitted | EID7555RAF 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) | —UNRESOLVED | Functional | D | Supports Gain Of Function | 2 | submitted | EID7652An 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) | —UNRESOLVED | Functional | D | Supports Gain Of Function | 5 | submitted | EID12982BRAF 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) | —UNRESOLVED | Functional | D | Supports Gain Of Function | 4 | submitted | EID12921BRAF 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 |