Review : p53 in the pathogenesis,diagnosis,and treatment of cancer

Objective. The cellular functions of p53, the conse quences of the loss of p53 function, and the potential impact of p53 in oncology are reviewed within the framework of an overview of the molecular basis of cancer and cell cycle control.

Data Sources. A MEDLINE search of articles from 1976 to the present was conducted using the terms p53 protein and p53 gene. The search was restricted to the English language. Oncology and molecular biology textbooks were used as additional references.

Data Extraction. We reviewed the literature to discuss the cellular function of p53, the mechanisms of p53 inactivation, the cellular consequences of the loss of p53 function, the role of p53 loss in tumori genesis, and the potential applications of this knowl edge.

Data Synthesis. p53 mutations are found in ~ 50% of human cancers. Knowledge of p53 functions and defects provides the basis for potential applica tions in the areas of cancer epidemiology, cancer diagnosis, and determination of prognosis. An under standing of the functions and defects of p53 also presents a host of opportunities for the design of novel cancer therapies. Therapeutic approaches be ing studied include the restoration of p53 by gene therapy, the alteration of mutant p53 expression by antisense therapy, and the use of p53 mutations as a target for directing therapy to cancer cells; some of these approaches are already under phase I investiga tion. As knowledge of p53 unfolds, additional thera peutic approaches will certainly be developed. The story of p53 illustrates that the manipulation of mo lecular interactions is a new frontier in therapeutics and offers an additional role for oncology pharmacy specialists.