BRAF and melanoma: Subsequent research showed that treatment with BRAF inhibitors alone causes resistance through a paradoxical signaling cascade mediated by MEK, leading to the development of MEK inhibitor therapies.1,4,5 The combination of BRAF and MEK inhibitor therapy has emerged as an optimal treatment of metastatic BRAF-mutated melanoma, with improved survival rates compared with monotherapy.6,7,8,9,10 A 2018 study11 found that the first BRAF and MEK inhibitor combination showed significant improvement in relapse-free survival in treating adjuvant stage III melanoma, which led to global approval.