While the addition of a SHP2i to MEKi augmented the durability of ERK inhibition and growth inhibition in BRAF V600E glioma cell lines, concerns have been raised over the tolerability of this combination.42 In an effort to improve tolerability, we evaluated the effects of combining SHP2i and BRAF inhibitor, which may have an improved therapeutic index, due to the opposing effects on phospho-ERK in normal tissues. The gene discussed is BRAF; the disease is central nervous system cancer.