p53: The Challenge of Linking Basic Science and Patient Management

Abnormalities of the p53 tumor suppressor gene are the single most common molecular abnormality seen in human cancer, being found in more than 50% of malignancies. Considerable evidence indicates that the product of this gene has critical roles in coordinating the response of cells to a diverse range of environmental stresses. Loss of p53 function is associated with loss of normal cell cycle control, diminished apoptosis, and genomic instability and is strongly associated with the neoplastic phenotype. We have a detailed knowledge of the biochemical properties of p53 and its activity as a transcription factor regulating diverse aspects of cellular function, but the in vivo physiological relevance of many of these remains uncertain. Nevertheless, p53 represents a highly significant potential target for novel therapeutic intervention; however, the further development of clinical applications and novel therapeutic strategies utilizing our knowledge of p53 is absolutely contingent upon bridging the gap between our biochemical understanding and our much less well-developed insights into the role of p53 in relevant physiological systems in vivo.