BRAF and metastatic melanoma: To overcome the development of resistance observed in patients treated with BRAF or MEK inhibitors as a single agent, it was believed that a more complete inhibition of the MAPK signaling pathway was required, so the combined therapy with trametinib and dabrafenib was approved by the FDA for the treatment of patients with BRAF V600E/K-mutant unresectable or metastatic melanoma in 2014.