Natural Modulators of the TP53 Pathway: Potential Herbal and Plant‐Derived Agents for Cancer Therapy

The transcription factor p53, often called the "guardian of the genome," is critical for preserving genomic integrity. Mutations in the TP53 gene are found in approximately half of all human malignancies, including breast, colon, lung, liver, prostate, bladder, and skin cancers. p53 is activated by a wide range of cellular stress signals and orchestrates specific cellular responses based on the context and nature of the stress. As a tumor suppressor, p53 controls cancer initiation and progression by regulating cell cycle arrest, apoptosis, senescence, and DNA repair. Beyond its classical role in genome surveillance, p53 is now recognized as a dynamic signaling hub whose functions can be therapeutically modulated in cancer. Natural products derived from medicinal plants represent a rich source for discovering and developing novel therapeutic and preventive agents against cancer. Several natural compounds have been reported to target mutant p53 in cancer cells, offering a potentially effective strategy for modulating the p53 signaling pathway. This review highlights recent advances in identifying and developing anticancer natural products that modulate the expression or activity of the p53 tumor suppressor gene for cancer treatment and prevention.