Exploiting the p53 Pathway for the Diagnosis and Therapy of Human Cancer

Abstract

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