Targeting MDM2 presents several challenges. One major issue is the development of resistance to MDM2 inhibitors, often through mutations in the p53 gene or overexpression of alternative p53 regulators such as MDM4. Additionally, due to the central role of p53 in normal cellular functions, reactivation of p53 can lead to toxicity in normal tissues. Therefore, the selective targeting of MDM2 in cancer cells while sparing healthy cells remains a significant challenge.
