We now reveal that the inhibition or silencing of EZH2 contributes to the enhancement of response to vemurafenib in resistant melanoma cells, that treatment with vemurafenib and EPZ suppresses genes which are involved in the regulation of mitosis and cell-cycle progression, and finally, that the effects mediated by the inhibition of EZH2 can be explained by the downregulation of PLK1. The gene discussed is EZH2; the disease is melanoma.