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BIOMARKER:

BRAF V600 wild-type

i
Other names: BRAF, B-raf proto-oncogene, B-raf proto-oncogene, Serine/threonine kinase, V-Raf murine sarcoma viral oncogene homolog B, Serine/threonine-protein kinase B-Raf, Proto-oncogene B-Raf, BRAF1, RAFB1, B-raf proto-oncogene Serine/threonine-protein kinase, Murine sarcoma viral (V-Raf) oncogene homolog B1, B-raf serine/threonine-protein, 94 KDa B-raf protein, B-RAF1
Entrez ID:
3ms
Effectiveness of 225Ac-Labeled Anti-EGFR Radioimmunoconjugate in EGFR-Positive Kirsten Rat Sarcoma Viral Oncogene and BRAF Mutant Colorectal Cancer Models. (PubMed, J Nucl Med)
Anti-CD20 [225Ac]Ac-macropa-rituximab was developed and used as a nonspecific radioimmunoconjugate. Compared with untreated mice, [225Ac]Ac-macropa-nimotuzumab more than doubled (16 vs. 41 d) the median survival of mice bearing SW620 xenografts. [225Ac]Ac-macropa-nimotuzumab is effective against KRAS mutant and BRAFV600E mutant CRC models.
Preclinical • Journal
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • DLD (Dihydrolipoamide Dehydrogenase)
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BRAF V600E • KRAS mutation • BRAF mutation • BRAF V600 • KRAS wild-type • BRAF wild-type • RAS wild-type • EGFR positive • BRAF V600 wild-type
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Rituxan (rituximab) • TheraCIM (nimotuzumab)
3ms
A Case of Response to Pembrolizmab in Unresectable MSI-High Transverse Colon Cancer (PubMed, Gan To Kagaku Ryoho)
Drug therapy with pembrolizumab was prescribed...Primary lesion turned almost undetectable, however the biopsy demonstrated residual tumor. Two months later, CT showed that the residual lymph nodes had also disappeared.
Journal • MSi-H Biomarker • PD(L)-1 Biomarker
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MSI (Microsatellite instability)
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BRAF V600E • MSI-H/dMMR • BRAF V600 • BRAF wild-type • RAS wild-type • BRAF V600 wild-type
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Keytruda (pembrolizumab)
5ms
Oncocytic Follicular Cell-Derived Thyroid Tumors With Papillary Growth Pattern: A Clinicopathologic Study of 32 Cases. (PubMed, Arch Pathol Lab Med)
Oncocytic thyroid tumors with papillary features can span a spectrum from benign hyperplastic, to encapsulated neoplastic, to invasive malignant lesions. Owing to their papillary features, it is important not to confuse them for other types of thyroid tumors, such as oncocytic papillary thyroid carcinoma.
Journal
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BRAF (B-raf proto-oncogene) • KRT19 (Keratin 19)
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BRAF V600E • BRAF V600 • BRAF wild-type • BRAF V600 wild-type
6ms
NIRVANA: Nivolumab Plus Radiotherapy in Advanced Melanoma (clinicaltrials.gov)
P2, N=72, Completed, Centre Hospitalier Universitaire de Nice | Unknown status --> Completed
Trial completion • Combination therapy • Metastases
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BRAF (B-raf proto-oncogene)
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BRAF mutation • BRAF V600 • BRAF wild-type • BRAF V600 wild-type
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Opdivo (nivolumab)
8ms
HASHIMOTO'S THYROIDITIS RESTRAINS THYROID CANCER PROGRESSION BY REMODELING TUMOR MICROENVIRONMENT (ATA 2023)
Precursor CD8Tex featuring ANXA1‐GZMH+ was the effector CD8Tex in PTC. Our analysis revealed the cellular mechanism of how HT and BRAFV600E mutation influence PTC prognosis, implicating HT and BRAFV600E mutation in optimizing the PTC classification system.
Late-breaking abstract
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CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • CXCL13 (Chemokine (C-X-C motif) ligand 13) • ANXA1 (Annexin A1) • GZMH (Granzyme H)
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BRAF V600E • BRAF V600 • BRAF wild-type • BRAF V600 wild-type
9ms
P2 data • Clinical Trial,Phase II • Journal
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BRAF (B-raf proto-oncogene) • RAS (Rat Sarcoma Virus)
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BRAF V600E • BRAF V600 • BRAF wild-type • RAS wild-type • BRAF V600 wild-type
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Erbitux (cetuximab) • Mektovi (binimetinib) • Braftovi (encorafenib)
10ms
The tyrosine kinase inhibitor lenvatinib inhibits anaplastic thyroid carcinoma growth by targeting pericytes in the tumor microenvironment. (PubMed, Thyroid)
Pericytes are enriched in ATC samples and may enhance tumor viability. Lenvatinib showed inhibitory effects on BRAFWT/V600E-ATC cells in the presence of pericytes. The presence of pericytes could be crucial for effective lenvatinib treatment. Degree of pericyte abundance may be an attractive prognostic marker in assessing pharmaco-therapeutic options. Effective, durable management of ATC will rely on an understanding not only of genetics but also on the role of the tumor microenvironment.
Journal
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BRAF (B-raf proto-oncogene)
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BRAF V600E • BRAF V600 • BRAF wild-type • BRAF V600 wild-type
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Lenvima (lenvatinib)
10ms
Low-Density Lipoprotein Receptor Is a Key Driver of Aggressiveness in Thyroid Tumor Cells. (PubMed, Int J Mol Sci)
The modulation of BRAF-V600E using vemurafenib-impaired LDLR expression decreased cellular proliferation. Our results suggest that LDLR regulation is cell line-specific, regulating the RAS/RAF/MAPK (MEK)/ERK pathway in the LDL-signaling cascade and where BRAF V600E can play a critical role. In conclusion, targeting LDLR and this downstream signaling cascade, could be a new therapeutic strategy for PTC with more aggressive behavior, especially in those harboring BRAF V600E.
Journal • Tumor cell
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BRAF (B-raf proto-oncogene) • MAPK1 (Mitogen-activated protein kinase 1)
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BRAF V600E • BRAF wild-type • BRAF V600 wild-type
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Zelboraf (vemurafenib)
12ms
The role of molecular testing in pancreatic cancer. (PubMed, Therap Adv Gastroenterol)
Genetic, epigenetic, and tumor microenvironment targets continue to be identified at an unprecedented pace, enabling PDA patients to be matched to targeted and immune therapeutics, including antibody-drug conjugates, and genetically engineered chimeric antigen receptor or T-cell receptor - T-cell therapies. In this review, we highlight clinically relevant molecular alterations and focus on targeted strategies that can improve patient outcomes through precision medicine.
Review • Journal • MSi-H Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • RET (Ret Proto-Oncogene) • NTRK (Neurotrophic receptor tyrosine kinase)
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BRAF V600E • KRAS mutation • MSI-H/dMMR • KRAS G12C • BRAF V600 • KRAS G12D • KRAS wild-type • BRAF wild-type • RET mutation • RAS wild-type • KRAS G12 • BRAF V600 wild-type • NTRK fusion
over1year
An Immunogenic Cell Death-Related Gene Signature Reflects Immune Landscape and Predicts Prognosis in Melanoma Independently of BRAF V600E Status. (PubMed, Biomed Res Int)
Thus, the ICD risk signature was closely associated with the tumor's immune microenvironment. Our results may provide insights to further individualize and improve precision therapeutic decision-making in BRAF V600E-mutant and WT melanoma.
Journal • Gene Signature • IO biomarker
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BRAF (B-raf proto-oncogene)
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BRAF V600E • BRAF V600 • BRAF wild-type • BRAF V600 wild-type
over1year
MRI-Based Texture Analysis for Preoperative Prediction of BRAF V600E Mutation in Papillary Thyroid Carcinoma. (PubMed, J Multidiscip Healthc)
The accuracy, sensitivity, specificity, PPV, and NPV were 0.776, 0.679, 0.905, 0.905, and 0.679 for the T2WI model at a cut-off value of 0.674; 0.755, 0.750, 0.762, 0.808, and 0.696 for the CE-T1WI model at a cut-off value of 0.573; 0.816, 0.893, 0.714, 0.806, and 0.833 for the combined model at a cut-off value of 0.420. MRI-based texture analysis could be a potential method for predicting BRAF V600E mutation in PTC preoperatively.
Journal
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BRAF (B-raf proto-oncogene)
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BRAF V600E • BRAF V600 • BRAF wild-type • BRAF V600 wild-type
over1year
X-linked inhibitor of apoptosis protein (XIAP) predicts disease-free survival in BRAFV600E mutant papillary thyroid carcinoma in middle eastern patients. (PubMed, Front Endocrinol (Lausanne))
XIAP expression is an independent predictor of prognosis in Middle Eastern PTC patients. Combination of XIAP expression and BRAFV600E mutation can synergistically improve the DFS prediction in PTC patients, which may help clinicians to establish the most appropriate initial care and long-term surveillance strategies.
Journal
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BRAF (B-raf proto-oncogene) • XIAP (X-Linked Inhibitor Of Apoptosis)
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BRAF V600E • BRAF V600 • BRAF wild-type • XIAP overexpression • BRAF V600 wild-type
over1year
TRIDENTE trial: A phase II study of rechallenge with encorafenib, binimetinib, and cetuximab in patients with RAS wild-type/BRAF V600E–mutant metastatic colorectal cancer. (ASCO-GI 2023)
Key eligibility criteria includes RAS WT/BRAF V600E mutant mCRC; ≥ 20 years old; ECOG PS 0-1; refractory or intolerant to at least one fluoropyrimidine-based regimen (including irinotecan or oxaliplatin); refractory or intolerant to anti-PD-1 antibody if patients with MSI-high; history of previous combination therapy containing ENCO + CET with at least partial response by RECIST v1.1; confirmed disease progression within 4 weeks after last administration of previous ENCO; ≥ 4 months of period between the last administration of previous ENCO and the start of study treatment. As of September 19, 2022, 8 patients have been enrolled. Clinical trial information: jRCTs031210511.
Clinical • P2 data • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker • Metastases
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BRAF (B-raf proto-oncogene) • RAS (Rat Sarcoma Virus)
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BRAF V600E • MSI-H/dMMR • BRAF V600 • BRAF wild-type • RAS mutation • RAS wild-type • BRAF V600 wild-type
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Erbitux (cetuximab) • Mektovi (binimetinib) • Braftovi (encorafenib) • oxaliplatin • irinotecan
over1year
P2 data • Clinical • Metastases
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BRAF (B-raf proto-oncogene)
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BRAF V600E • BRAF V600 • BRAF wild-type • RAS mutation • RAS wild-type • BRAF V600 wild-type
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Guardant360® CDx
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Erbitux (cetuximab) • Mektovi (binimetinib) • Braftovi (encorafenib)
over1year
Estimated sensitivity profiles of lung cancer specific uncommon BRAF mutants towards experimental and clinically approved kinase inhibitors. (PubMed, Toxicol Appl Pharmacol)
All the uncommon mutants displayed higher sensitivity than both the wild type and BRAF-V600E towards PLX 8394 and LSN3074753...Notably, molecular dynamic (MD) simulation revealed that increased number of interactions caused enhanced sensitivity of G469R and N581S towards sorafenib. RAF kinase inhibitors were further classified into two groups as per their selectivity (Group I: BRAF-V600E-selective and Group II: CRAF-selective) based on which potential mutation-wise combinations of RAF kinase inhibitors were proposed to overcome resistance. Based on computational inhibitor sensitivity profiles, appropriate treatment strategies may be devised to prevent or overcome secondary drug resistance in lung cancer patients with uncommon mutations.
Journal
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene)
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BRAF V600E • KRAS mutation • EGFR mutation • BRAF mutation • BRAF V600 • BRAF V600K • BRAF wild-type • EGFR mutation + KRAS mutation • BRAF G469A • BRAF G466A • BRAF G469R • BRAF V600 wild-type
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sorafenib • LY3009120 • plixorafenib (FORE-8394)
almost2years
COLSTAR: Randomized, open-label, multicentre, phase III study comparing futuximab/modotuximab plus trifluridine/tipiracil to trifluridine/tipiracil in KRAS/NRAS and BRAF wild type (wt) metastatic colorectal cancer (mCRC) previously treated with both standard and anti-EGFR treatment (ESMO 2022)
Main eligibility criteria include KRAS/NRAS (exons 2, 3 and 4) and BRAF wt (V600E mutation) (double negative; DN) assessed by centralized analysis of ctDNA at screening, and previous treatment with at least 2 regimens including fluoropyrimidine, irinotecan, oxaliplatin, at least one anti-VEGF (bevacizumab, aflibercept, ramucirumab, regorafenib) and at least one anti-EGFR mAb (cetuximab or panitumumab) for ≥4 months. The key secondary endpoint is OS in the triple-negative (KRAS/NRAS, BRAF, and EGFR-ECD wt) population (part 2). A group sequential design with 3 interim analyses (IA) will allow to stop the trial prematurely for futility at each IA as well as for efficacy at last IA.
Clinical • P3 data
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RAS (Rat Sarcoma Virus)
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BRAF V600E • KRAS wild-type • BRAF wild-type • NRAS wild-type • KRAS exon 2 mutation • BRAF V600 wild-type • BRAF wild-type + NRAS wild-type
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Avastin (bevacizumab) • Erbitux (cetuximab) • Vectibix (panitumumab) • Stivarga (regorafenib) • Cyramza (ramucirumab) • oxaliplatin • irinotecan • Lonsurf (trifluridine/tipiracil) • futuximab/modotuximab (S95026)
2years
Comparative analysis of microsatellite instability-high (MSI-H) BRAF V600E-mutated versus MSI-H BRAF wild type colorectal cancers (CRC), including tumor microenvironment (TME), associated genomic alterations, and immunometabolomic biomarkers. (ASCO 2022)
MSI-H/dMMR BRAFV600E CRCs undergo broad metabolic reprogramming (e.g., glycerophospholipidgalactose, nucleotide). A rise in lipid metabolism, particularly with NK inflammation, suggests that BRAFV600Emutated tumors may be associated with a non-classical immune component. BRAFV600E and BRAFwt CRCs exhibited similar NTB and T cell infiltration, suggesting that both are likely to benefit from immune checkpoint inhibitors.
Tumor Mutational Burden • Microsatellite instability • BRCA Biomarker • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • CD8 (cluster of differentiation 8) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • B2M (Beta-2-microglobulin) • CD4 (CD4 Molecule)
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PD-L1 expression • TP53 mutation • BRAF V600E • TMB-H • MSI-H/dMMR • BRAF V600 • BRAF wild-type • MSH6 mutation • BRAF V600 wild-type
2years
A randomized, double-blind phase 2 evaluation of the anti-IL-8 monoclonal antibody BMS-986253 + nivolumab + ipilimumab vs nivolumab + ipilimumab in patients with advanced melanoma that progressed on/after anti-PD-(L)1 therapy (AACR 2022)
Secondary objectives include PFS by BICR in all randomized patients, overall response rates by BICR per RECIST v1.1, overall survival, safety, pharmacokinetic profile, immunogenicity of BMS-986253, and associations of baseline factors with response. Recruitment will continue until ≈170 patients are enrolled.
Clinical • P2 data • PD(L)-1 Biomarker • IO biomarker
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BRAF (B-raf proto-oncogene) • CXCL8 (Chemokine (C-X-C motif) ligand 8)
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BRAF V600E • BRAF V600 • BRAF wild-type • CXCL8 elevation • BRAF V600 wild-type
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Opdivo (nivolumab) • Yervoy (ipilimumab) • BMS-986253
over2years
Potential benefit of treatment with MEK inhibitors and chemotherapy in BRAF-mutated KRAS wild-type pancreatic ductal adenocarcinoma patients: a case report. (PubMed, Cold Spring Harb Mol Case Stud)
This is the first case report of a 60-yr-old female who underwent therapy for metastatic pancreatic cancer with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX). The patient has achieved a complete response (CR) to a combination of gemcitabine, nab-paclitaxel, and cobimetinib. It has been 16 mo since the start of the treatment, and the patient continues to demonstrate a complete durable response both serologically and radiologically.
Clinical • Journal
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • MAP2K2 (Mitogen-activated protein kinase kinase 2)
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BRAF V600E • KRAS mutation • BRAF mutation • BRAF V600 • KRAS wild-type • BRAF wild-type • RAS wild-type • MAP2K1 mutation • BRAF V600 wild-type
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gemcitabine • 5-fluorouracil • Cotellic (cobimetinib) • albumin-bound paclitaxel • oxaliplatin • irinotecan • leucovorin calcium