Exploiting the p53 pathway for the diagnosis and therapy of human cancer.

After 26 years of research and the publication of 38,000 papers, our knowledge of the p53 human tumor suppressor protein is impressive. Over half of all human cancers have mutations in the p53 gene, and the p53 pathway in animal models dramatically regulates the cellular response to ionizing radiation and chemotherapeutic drugs. The ability to translate this knowledge to patient benefit is, however, still in its infancy. The many approaches to determining the status of the p53 pathway in human tumor biopsy samples and the attempts to develop p53-selective therapies are described. A great deal of our knowledge of the p53 system remains incomplete, and the issue of how to best conduct translational research in cancer is debated using the difficulties around the p53 system as an example. The need for a more unified and coordinated approach to critical technological developments and clinical trial protocols is discussed.