Because TOP2A CTR can increase MDM4‐p53 binding through interacting with the auto‐inhibitory element, targeting the interaction between TOP2A CTR and MDM4 auto‐inhibitory element may represent an alternative strategy to activate p53 in cancer cells by modulating MDM4 activity; simultaneously, targeting this interaction may result in specific downregulation of TOP2A. The gene discussed is MDM4; the disease is cancer.