According to our finding that genotoxic stress-triggered β-catenin/JDP2/PRMT5 complex formation resulted in WDR5/MLL methyltransferase complex-mediated restoration of GSH homeostasis, we demonstrated that combined treatment with OICR-9429, an antagonist of the WDR5-MLL interaction, could inhibit the GSH-metabolism reestablishing and lead to a lethal increase in the already-elevated levels of ROS in genotoxic chemotherapeutics-treated cancer cells. This evidence concerns the gene JDP2 and cancer.