BRAF and melanoma: To date, four MEK inhibitors have been approved by the FDA, including trametinib for melanoma in 2013 [233], cobimetinib for BRAF-mutated advanced melanoma in 2015 [234], binimetinib for unresectable or metastatic melanoma with BRAFV600E or BRAFV600K mutations in 2018 [235], and selumetinib, approved in 2020 for type 1 neurofibromatosis [236].