The Development of p53-Targeted Therapies for Human Cancers

p53 plays a critical role in tumor suppression and is the most frequently mutated gene human cancers. Most mutants (mutp53) are missense mutations thus expressed In cancers that retain wtp53, wtp53 activities downregulated through multiple mechanisms. For example, overexpression of negative regulators p53, MDM2/MDMX, can also efficiently destabilize inactivate wtp53. Therefore, both mutp53 have become promising intensively explored therapeutic targets for cancer treatment. Current efforts include development small molecule compounds to disrupt interaction between MDM2/MDMX expressing restore wtp53-like activity mutp53. addition, synthetic lethality approach has been applied identify signaling pathways affected by dysfunction, which, when targeted, lead cell death. While an intensive search p53-targeted therapy produced potential candidates with encouraging preclinical efficacy data, it remains challenging develop such drugs good safety profiles. A more in-depth understanding mechanisms action these p53-targeting will help overcome challenges.