RB1 and cancer: Cancer cells can evade mechanisms mediated by the action of tumor suppressor genes.37,55 Notably, RB (retinoblastoma-associated) and p53 proteins are two main tumor suppressors, operating in various ways to modulate cells to maintain homeostasis.201–203 Defects in function of the RB pathway result in persistent cell proliferation due to dysregulation of gatekeepers of cell-cycle progression.204 By contrast, p53 senses intracellular stress, such as energy stress, genotoxic stress, and oxidative stress, preventing further cell-cycle progression until homeostasis returns to normal.