Mechanisms of p53 inactivation in TP53 wild type tumors and factors affecting sensitivity to MDM2 inhibitors
The research group led by Dr Roberta Maestro demonstrated that the overexpression of the protein Twist, detectable in a large fraction of sarcomas but also in a fraction of carcinomas, facilitates the MDM2-mediated degradation of p53 by making p53 more susceptible to MDM2 attack. The p53:MDM2 interplay is the target of a number of compounds currently under clinical trials. These compounds (MDM2i) are aimed at alleviating p53 from MDM2-mediated degradation and hence at restoring the p53 tumor suppressive activity. Maestro and coworkers gathered data indicating that the expression of Twist may significantly impact on the activity of these drugs.