MDM2 and neoplasm: However, McCormick [61] and others [62]later reported that ONYX-015 [60] replicates efficiently in p53+ tumor cells [63], possibly due to the tumors inhibiting p53 activity through other mechanisms such as overexpression of the endogenous p53 inhibitor, Mdm2, or the loss of p14ARF, which downregulates Mdm2 (Figure 2).