p53, the Guardian of the Genome

p53, often referred to as the “guardian of the genome,” is a crucial tumor suppressor protein that regulates cell-cycle progression, apoptosis, and DNA repair. Its role in maintaining genomic stability is central to the DNA damage response (DDR), which activates signaling cascades that halt cell-cycle progression, allowing time for DNA repair or triggering apoptosis when damage is irreparable.

Drug discovery efforts targeting p53 focus on restoring tumor-suppressive function in cancers with TP53 mutations. Key strategies include reactivating mutant p53, such as with APR-246, inhibiting the MDM2–p53 interaction to stabilize p53, and activating alternative pathways in p53-deficient cells. Mutant-specific small molecules, gene-therapy approaches, and immunotherapy strategies are also being explored to counteract dysfunctional p53 signaling.

Learn more from our poster presented at the 7th Annual DDR Inhibitor Summit ↗.

A Comprehensive p53 Drug Discovery Platform: From Target-Based Assays to In Vivo Models ↗