Downstream of MEK, increased ERK1/2 kinase activity leads to acquired drug resistance (Morris et al., 2013; Sanchez et al., 2019; Wagle et al., 2014); however, ERK1/2 inhibitors (ERK1/2i) have shown limited clinical activity as single agents in melanoma, including in a patient with non-E/K V600 BRAF mutant CM, and in other solid tumors (Janku et al., 2020; Moschos et al., 2018; Sullivan et al., 2018). This evidence concerns the gene BRAF and melanoma.