Playing POLO-like kinase in NRAS mutant melanoma

NRAS-mutant melanomas are extremely aggressive and highly resistant to currently available therapeutic modalities. Hence, new targets and therapeutic strategies for NRAS-driven melanomas are needed. As blocking NRAS directly has not been possible thus far, targeting downstream NRAS effectors, such as MEK, is being evaluated as an alternative therapeutic approach. However, blocking this pathway alone has limited efficacy. In this issue, Posch et al. report on a combination approach co-targeting PLK1 and MEK in NRAS-mutant melanomas. This combination triggers a dual blockade of the cell cycle machinery, leading to apoptosis, and it may provide a new strategy to treat NRAS-mutant melanoma.