Variations of BRAF mutant allele percentage in melanomas
نویسندگان
چکیده
منابع مشابه
Will Hsp90 inhibitors prove effective in BRAF-mutant melanomas?
The RAF inhibitor vemurafenib has unprecedented activity in BRAF-mutant melanomas, but resistance invariably develops. As Hsp90 is required for the stability of several of the oncoproteins that mediate RAF inhibitor resistance, inhibitors of this cellular chaperone may be effective in patients with intrinsic or acquired resistance to RAF inhibitors.
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BACKGROUND Somatic mutations of BRAF or NRAS activating the MAP kinase cell signaling pathway are present in 70% of cutaneous melanomas. The mutant allele frequency of BRAF V600E (M%BRAF) was recently shown to be highly heterogeneous in melanomas. The present study focuses on the NRAS Q61 mutant allele frequency (M%NRAS). METHODS Retrospective quantitative analyze of 104 NRAS mutated melanoma...
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Large-scale, unbiased combinatorial drug screening has been used to identify effective genotype-selective therapeutic combinations that show promising activity in preclinical models of mutant BRAF andRAS melanoma that are resistant to the clinical BRAF inhibitor vemurafenib.
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IMPORTANCE BRAF inhibitors have become the standard of care in metastatic BRAF-mutant melanomas. Compared with chemotherapies, BRAF inhibitors improve overall and disease-free survival and speed the recovery of symptomatic patients with metastatic disease. The most worrisome finding is the possible development of resistance to new malignant tumors. OBSERVATIONS A patient in her 30s developed ...
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The development of vemurafenib resistance limits the long-term efficacy of this drug for treatment of metastatic melanomas with the (V600E)BRAF mutation. Inhibition of downstream MAPK signaling with vemurafenib induces apoptotic cell death mediated by caspase-3, suggesting that addition of a procaspase-3 activator could enhance anticancer effects. Here, we show that the combination of PAC-1, a ...
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ژورنال
عنوان ژورنال: BMC Cancer
سال: 2015
ISSN: 1471-2407
DOI: 10.1186/s12885-015-1515-3