In addition, in order to enhance the tumor heterogeneity and genetic complexity, which constitute notable features of human cancers, we adopted models in which both endogenous copies of the p53 tumor suppressor have been substituted by an impaired p53 (p53ER/ER), allowing for accelerated mutational rate and the development of more aggressive and heterogeneous tumors [25, 26]. Here, TP53 is linked to neoplasm.