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Through a somatic point mutation at codon V600, valine is substituted by glutamate (BRAF V600E ), which is thought to mimic regulatory phosphorylation in the activation segment of the protein kinase domain ( V600E -mutated kinase monomers constitutively activate the downstream MAPK-ERK signaling pathway, regardless of any external stimuli and independent of upstream Ras ( Due to the high incidence of BRAF V600E in several solid cancers, small molecule inhibitors against BRAF V600E have been developed and have been actively tested in the clinic ( V600E and MEK inhibitor combination therapy (e.g., dabrafenib+trametinib) has been tested in the clinic against glioma and clinical response rates of 70% and 33% have been observed amongst adults with low- and high-grade glioma, respectively