Continued oncogenic signaling in the initial growth phase prompts the activation of tumor suppressive signaling via activation of the p16INK4a/p14ARF–RB–p53 cell cycle and cell stress pathways (Fig. 2), slowing tumor growth and transitioning a majority of cells with intact pathways into a terminal state called oncogene-induced senescence [43]. This evidence concerns the gene RB1 and neoplasm.