The same group also identified FOXO3 as a key mediator of the ERK- and Akt-mediated regulation of glioblastoma stem cells.19 And FOXO3 is activated in colorectal CSCs and non-CSCs upon inhibition of the Akt and ERK pathways by ONC201/TIC10.20 Our study demonstrate here that simultaneously targeting an epigenetic mediator and an epigenetic modulator, by dual inhibiting OCT4 and AKT, can have significantly improved efficacies over single treatment in suppressing the propagation of CSCs as well as the entire bulk of differentiated cancer cells. The gene discussed is POU5F1; the disease is cancer.