Tumor protein p53 pathway (p53 pathway)

The tumor suppressor p53 pathway is a central cellular regulatory network orchestrated by the transcription factor p53, encoded by the TP53 gene, which is often called the "guardian of the genome". Upon cellular stress such as DNA damage, oncogene activation, or hypoxia, p53 is stabilized and activates genes involved in cell cycle arrest, DNA repair, apoptosis, senescence, autophagy, and metabolic control, thereby preventing the proliferation of cells with damaged genomes. Mutations in TP53 are extremely common in human cancers, and loss of p53 function is a major driver of tumorigenesis. Targeting the p53 pathway therapeutically includes strategies to restore p53 activity in cancers that harbor its loss or mutation, or to modulate its network interactions (such as MDM2 inhibition). While drugs targeting the p53 pathway hold great promise, therapeutic manipulation must balance anti-tumor efficacy with the need to avoid deleterious effects on normal tissue homeostasis and regeneration.

Other names

p53 signaling pathwayTP53 pathwayp53 networkp53 tumor suppressor pathwayguardian of the genome pathway

Activation of wild-type p53: Drugs increase functional p53 protein by disrupting negative regulation (e.g., MDM2 antagonists). Restoration/reactivation of mutant p53: Drugs that refold or stabilize mutant p53 to restore tumor suppressor function. Indirect activation (e.g., chemotherapy, radiation): Induce DNA damage, triggering p53 activation.