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Taneous cells, where type I BRAF inhibitors increase (or do not change) MAPK signaling in normal cells, while they efficiently block the MAPK pathway downstream of oncogenic BRAF V600. On the contrary, MEK inhibitors can equally block the MAPK pathway downstream of both oncogenic and wild type BRAF. This lack of differentiation most likely causes the dose limiting toxicities (DLT) at exposures in
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Mutants (sensitive: M207; resistant: M244) and BRAF mutants (sensitive: M229 and M249; resistant: M233 and M263) were cultured with 50 nM and 500 nM of TAK733 for 48 hours and stained with DAPI for cell cycle analysis.Discussion Initial data testing MEK inhibitors in melanoma cell lines suggested a high level and selective sensitivity in BRAF V600E mutant melanoma cell lines, with low sensitivity
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