MDM2, MDMX and p53 in oncogenesis and cancer therapy
Cet article passe en revue les perspectives offertes par le ciblage des protéines MDM2 et MDMX, qui exercent une activité oncogénique en inhibant p53, pour le développement de thérapies ciblées des cancers
The MDM2 and MDMX (also known as HDMX and MDM4) proteins are deregulated in many human cancers and exert their oncogenic activity predominantly by inhibiting the p53 tumour suppressor. However, the MDM proteins modulate and respond to many other signalling networks in which they are embedded. Recent mechanistic studies and animal models have demonstrated how functional interactions in these networks are crucial for maintaining normal tissue homeostasis, and for determining responses to oncogenic and therapeutic challenges. This Review highlights the progress made and pitfalls encountered as the field continues to search for MDM-targeted antitumour agents.