Targeting MDM2 for the development of a new cancer therapy: progress and challenges

For much of the past 20 years, MDM2 has been pursued as a cancer therapeutic target. Small molecule inhibitors that block the MDM2-p53 protein-protein interaction (MDM2 inhibitors) have been developed and a number of them have been evaluated in clinical trials for cancer treatment. Notwithstanding various setbacks, several MDM2 inhibitors have now progressed into late-stage clinical development. New strategies have also been developed to enhance the efficacy of MDM2 inhibitors and to mitigate their on-target toxicity. In this review, we summarize the progress and challenges in the development of a MDM2 targeted therapy.