Fundamentals and emerging frontiers in p53-targeted drug development

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• The p53 protein is a critical tumor suppressor involved in cell cycle regulation, DNA repair, and apoptosis.
• Mutations or inactivation of the p53 gene occur in over 50% of human cancers, promoting tumorigenesis and drug resistance.
• Targeting p53 is a key strategy in anticancer drug development, but faces challenges like diverse mutation types and resistance.

Purpose of the Study:

• To systematically review the fundamental theories and cutting-edge advances in p53-targeted drug development.
• To analyze the research history and clinical translation of small-molecule drugs targeting p53.
• To discuss the prospects of gene therapy, immunotherapy, CRISPR, and PROTAC technologies for p53-targeted cancer treatment.

Main Methods:

• Literature review of p53 structure, function, and mutation-induced carcinogenesis.
• Analysis of small-molecule drugs (e.g., APR-246) and their clinical status.
• Exploration of gene therapy, immunotherapy, CRISPR, and PROTAC technologies for p53-targeted therapies.

Main Results:

• p53 mutations are a significant driver of cancer development and drug resistance.
• Various therapeutic strategies are being developed to target p53, including small molecules, gene therapy, and novel technologies.
• Emerging approaches like CRISPR and PROTAC offer new avenues for precise p53-targeted drug development.

Conclusions:

• Developing effective p53-targeted drugs requires addressing diverse mutation types and overcoming drug resistance.
• Gene therapy, immunotherapy, CRISPR, and PROTAC technologies show promise for future p53-targeted cancer treatments.
• This review provides a theoretical basis and guidance for precise p53-targeted drug development and clinical translation.