TP53 and cancer: There are a few reasons for this: in addition to robust side effects such as thrombocytopenia [31,32] and gastrointestinal toxicity associated with Mdm2 experimental drugs [30], cancer cells were able to adapt to the prolonged therapy by enhancing the expression of other p53-targeting E3 ligases (Pirh2, WWP1, etc.)[33], higher efflux of Mdm2 inhibitors, and their increased metabolic degradation [11].