Wild type p53 reactivation: from lab bench to clinic

Area of Science:

• Oncology
• Molecular Biology
• Cancer Genetics

Background:

• The p53 tumor suppressor is frequently inactivated in various cancers.
• Reconstituting p53 function has shown potential in suppressing established tumor growth in preclinical models.
• This highlights p53 reactivation as a promising anti-cancer strategy.

Purpose of the Study:

• To review recent advancements in developing small molecules for p53 reactivation.
• To discuss the impact of p53 functions on tumor prevention and eradication.
• To analyze the role of p53 cofactors and cellular environment in clinical applications of p53 reactivation.

Main Methods:

• Review of recent scientific literature on p53 reactivation strategies.
• Focus on small molecules targeting p53 inhibitors (Mdm2, MdmX) and their regulators.
• Analysis of studies investigating p53 cofactors and cellular environment.

Main Results:

• Development of small molecules that block p53 inhibitors (Mdm2, MdmX) is progressing.
• Different p53 functions have varying impacts on tumor prevention and eradication.
• The role of p53 cofactors and cellular environment influences biological responses to p53 reactivation.

Conclusions:

• Small molecule-based p53 reactivation is a developing therapeutic strategy for cancer.
• Understanding p53's diverse functions is crucial for optimizing anti-cancer treatments.
• Further research into p53 reactivation, considering cofactors and cellular context, is essential for clinical translation.