This disclosure provides methods and strategies for inhibiting the growth of TP53 wild-type cancer cells, comprising contacting the cell with 2′,2′-difluoro-5-aza-2′-deoxycytidine or a 2′,2′-difluoro-5-aza-2′-deoxycytidine prodrug. Also provided are related methods for treating a cancer characterized by having wild-type TP53 in a subject in need thereof.