Sertraline significantly inhibited melanoma cell proliferation in a dose‐dependent mannerIt downregulated the Akt signaling pathwaySertraline induced ER stress, leading to apoptosis in melanoma cellsIn vivo, sertraline monotherapy modestly reduced melanoma tumor growth, but the effect was not statistically significantThe study suggests that sertraline may enhance the efficacy of existing melanoma treatments by inhibiting Akt and inducing ER stress. This evidence concerns the gene AKT1 and melanoma.