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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