In relation to neuroendocrine characteristics and t-NEPC, combined double knockout of tumor suppressors PTEN and RB1 or triple knockout of PTEN, RB1 and TP53 in mouse models reveal phenotypic plasticity and prostate cancer resistance to therapeutics, exhibit stem-like and neuroendocrine differentiation features and loss of AR activity [10,13,42]. This evidence concerns the gene TP53 and Familial prostate cancer.