Unpicking the combination lock for mutant BRAF and RAS melanomas.
نویسندگان
چکیده
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.
منابع مشابه
Genotype-selective combination therapies for melanoma identified by high-throughput drug screening.
UNLABELLED Resistance and partial responses to targeted monotherapy are major obstacles in cancer treatment. Systematic approaches to identify efficacious drug combinations for cancer are not well established, especially in the context of genotype. To address this, we have tested pairwise combinations of an array of small-molecule inhibitors on early-passage melanoma cultures using combinatoria...
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Although activating BRAF/NRAS mutations are frequently seen in melanomas, they are not sufficient to drive malignant transformation and require additional events. Frequent co-occurrence of mutations in the promoter for telomerase reverse transcriptase (TERT), along with BRAF alterations, has recently been noted and correlated with poorer prognosis, implicating a functional link between BRAF sig...
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Malignant melanoma is associated with poor clinical prognosis; however, novel molecular and immune therapies are now improving patient outcomes. Almost 50% of melanomas harbor targetable activating mutations of BRAF that promote RAS-RAF-MEK-ERK pathway activation and melanoma proliferation. Recent evidence also indicates that melanomas bearing mutant BRAF may also have altered immune responses,...
متن کاملNumber of nevi and early-life ambient UV exposure are associated with BRAF-mutant melanoma.
Malignant melanomas often contain BRAF or NRAS mutations, but the relationship of these mutations to ambient UV exposure in combination with phenotypic characteristics is unknown. In a population-based case series from North Carolina, 214 first primary invasive melanoma patients in the year 2000 were interviewed regarding their risk factors. Ambient solar UV exposures were estimated using resid...
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عنوان ژورنال:
- Cancer discovery
دوره 3 1 شماره
صفحات -
تاریخ انتشار 2013