Starting from the mechanism demonstrated in our previous work in follicular thyroid tumors, in which the inhibition of p90RSK triggers a decrease in cell proliferation and the activation of apoptosis through the MDM2/p53 pathway, here, we demonstrate that the inhibition of the p90RSK/MDM2/p53 pathway is critical in inducing a blockade of proliferation and apoptosis by regulating p53wt levels through the stabilization of MDM2 in selected tumors with constitutively activated MAPKs such as melanoma and lung cancer. This evidence concerns the gene RPS6KA1 and melanoma.