It has been previously demonstrated that small molecule inhibitors of MDM2 and PPM1D synergize to elicit p53-dependent cell death in diverse cell types29–33, and we have previously shown that gain-of-function PPM1D mutations are mutually exclusive with p53 mutations in thyroid carcinoma2, suggesting that PPM1D restrains p53 activity in this cancer type. Here, MDM2 is linked to cancer.