Exploiting the p53 Pathway for Therapy.

The excitement around the entry into the clinic of the first generation of p53-specific drugs has become muted as the hoped-for dramatic clinical responses have not yet been seen. However, these pioneer molecules have become exceptionally powerful tools in the analysis of the p53 pathway and, as a result, a whole spectrum of new interventions are being explored. These include entirely novel and innovative approaches to drug discovery, such as the use of exon-skipping antisense oligonucleotides and T-cell-receptor-based molecules. The extraordinary resources available to the p53 community in terms of reagents, models, and collaborative networks are generating breakthrough approaches to medicines for oncology and also for other diseases in which aberrant p53 signaling plays a role.