Awakening the "guardian of genome": reactivation of mutant p53

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• The tumor suppressor protein p53 is crucial for preventing cancer by inducing cell-cycle arrest, apoptosis, or senescence.
• Mutations in the p53 gene occur in approximately 50% of human cancers, leading to altered protein conformation, increased stability, and oncogenic activity.
• Mutant p53 accumulates in the nucleus, interacts with oncoproteins, and promotes carcinogenesis, posing significant therapeutic challenges.

Purpose of the Study:

• To comprehensively review molecules capable of reactivating mutant p53.
• To focus on the molecular mechanisms underlying the restoration of normal p53 function and transcriptional activity.
• To discuss strategies for overcoming therapeutic challenges posed by mutant p53.

Main Methods:

• Literature review of modern scientific techniques and discoveries.
• Analysis of various compounds, including small molecules, peptides, and phytochemicals.
• Focus on molecular mechanisms of mutant p53 reactivation.

Main Results:

• Identification of diverse molecules (small molecules, peptides, phytochemicals) that can reactivate mutant p53.
• Understanding of molecular mechanisms through which these compounds restore p53's native-like structure and transcriptional activity.
• Exploration of approaches to restore p53 family member functions.

Conclusions:

• Reactivating mutant p53 holds promise for cancer therapy.
• Various small molecules, peptides, and phytochemicals show potential in restoring p53 function.
• Further research into molecular mechanisms is essential for developing effective therapies against p53-mutated cancers.