This reprogramming involves the suppression of luminal differentiation markers, thereby facilitating the loss of AR dependency and promoting a basal-like or NE phenotype.51,54 Targeting key regulators, such as Sox2, or the pathways activated by the combined loss of RB1, TP53 and Pten, may offer new therapeutic strategies to overcome resistance and prevent tumor evolution in advanced prostate cancer. The gene discussed is RB1; the disease is prostate cancer.