Recent studies in various prostate cancer mouse models support an active role of TP53 mutations in prostate cancer progression: (i) the loss of TP53, together with PTEN mutations and/or RB1 loss, was found to shape cell lineage plasticity and reprogramming, thus promoting resistance to androgen deprivation [295,296], and (ii) loss-of-function of TP53 promotes the development of castration-resistance in prostate cancer cells through two different mechanisms involving potentiation of androgen-independent cell growth and promoting genome instability [298]. Here, RB1 is linked to prostate cancer.