BRAF and melanoma: In fact, it has been shown that increased expression of AKT1 and activation of AKT1 via phosphorylation promotes melanoma proliferation and metastasis,54,55 is associated with reduced melanoma patient survival,56,57 and mediates resistance to BRAF inhibitor therapy.58,59 The observed reduction of AKT1 expression via treatment with vemurafenib + tretinoin combination may partially explain the drug combination’s synergistic action in reducing cell proliferation in BRAF-mutant A375 cells in this study.