نتایج جستجو برای: braf
تعداد نتایج: 7505 فیلتر نتایج به سال:
UNLABELLED Mutationally activated BRAF(V600E) cooperates with PTEN silencing in the conversion of normal melanocytes to metastatic melanoma cells, but the mechanism underlying this cooperation is poorly understood. Here, the consequences of pharmacologic blockade of BRAF(V600E) or phosphoinositide 3-kinase (PI3K) signaling were explored using pathway-targeted inhibitors and a panel of human BRA...
BACKGROUND The BRAF inhibitors vemurafenib and dabrafenib are currently the standard treatment for metastatic melanoma with BRAF V600 mutations. However, given the rarity of noncutaneous melanoma, including acral and mucosal subtypes, the efficacy of BRAF inhibitors for this subset of patients has not been extensively investigated. Acquired resistance generally appears 6 to 8 months after treat...
Mutational activation of BRAF leading to expression of the BRAF oncoprotein was recently identified in a high percentage of specific hematopoietic neoplasms in monocyte/histiocyte and mature B-cell lineages. Although BRAF is a driver oncoprotein and pharmacologic target in solid tumors such as melanoma, lung, and thyroid cancer, it remains unknown whether BRAF is an appropriate therapeutic targ...
Somatic mutations in BRAF occur in two thirds of cutaneous melanomas, leading to the activation of the RAF-MEK-ERK signalling pathway. Preclinical studies of BRAF mutations showed that inhibition of BRAF led to melanoma cell proliferation inhibition and apoptosis induction in vitro and blockade of melanoma xenograft growth in vivo. Clinical studies of BRAF inhibitors in BRAF-mutated metastatic ...
V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) is a serine/threonine-specific protein kinase that is mutated with high frequency in cutaneous melanoma, and many other cancers. Inhibition of mutant BRAF is an attractive therapeutic approach for the treatment of melanoma. A triarylimidazole BRAF inhibitor bearing a phenylpyrazole group (dimethyl-[2-(4-{5-[4-(1H-pyrazol-3-yl)-phenyl]-4-pyri...
PURPOSE V600E is the most common activating BRAF mutation in colorectal carcinomas (CRCs). It is a crucial biomarker for patient selection and response to targeted therapy with BRAF V600E inhibitors. Previous studies using immunohistochemistry (IHC) have shown different results. In this study, we evaluated the IHC expression of the mutated BRAF protein in archival material from CRC specimens an...
Growth factor-induced signalling leads to activation of members of the Ras family and subsequent stimulation of different Raf isoforms. Within the mechanism of Raf activation, two isoforms of Raf, cRaf and BRaf, may cooperate. We investigated the relationship between cRaf and BRaf and found that active Ras induced heterodimerization of cRaf and BRaf, an effect that was dependent on the serine r...
The rationale for using small molecule inhibitors of oncogenic proteins as cancer therapies depends, at least in part, on the assumption that metastatic tumors are primarily clonal with respect to mutant oncogene. With the emergence of BRAF(V600E) as a therapeutic target, we investigated intra- and inter-tumor heterogeneity in melanoma using detection of the BRAF(V600E) mutation as a marker of ...
INTRODUCTION Since introduction of BRAF and MEK inhibition therapy, there has been a significant improvement in response rates, overall survival, and progression-free disease in melanoma patients. Combined BRAF and MEK inhibition, compared with BRAF inhibition alone, has shown to delay the emergence of resistance in patients suffering from BRAF V600emutated advanced melanoma. It has become the ...
The NRAS and BRAF genes are frequently mutated in melanoma, suggesting that the NRAS-BRAF-MEK-ERK signaling pathway is an important target for therapy. Two classes of drugs, one targeting activated BRAF and one targeting MEK, are currently undergoing clinical evaluation. We have analysed the NRAS and BRAF mutational status of a series of 44 early passage lines developed from New Zealand patient...
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