TP53 and neoplasm: In tumor cells, checkpoints are often overridden by oncogenic activation of proliferative signaling via PI3K-Akt [79, 80] and/or loss-of-function of gatekeeper genes like TP53. It follows that with increasing RT fraction number, ionizing radiation leads to a decreasing fraction of normal cells in sensitive S and M phases while tumor cells are mostly unaffected by redistribution.