MDM2 and cancer: Apart from inhibition of p53-MDMs interactions, other approaches have been used in order to reactivate wild-type p53 including targeting MDM2 E3 ligase, sirtuins, the calcium-binding protein S100B, etc. In addition, p53 function perturbations are also observed in cancers as a result of point mutations to the TP53 gene, representing the most frequent mutated gene observed in human cancers.