Molecular "rehabilitation" by rational drug targeting: The challenge of p53 in cancer treatment

The p53 tumor suppressor protein is a pivotal molecule in the protection ag ainst carcinogenesis and Is inactivated in a plethora of human neoplasms. p 53 prevents the accumulation of genomic alterations by inducing cell-cycle arrest or programmed cell death in response to genotoxic signals such as DN A damage and stress. In as much as p53 is a key modulator of cell prolifera tion, tight regulation of its function is critical for normal growth and ho meostasis of cells and tissues. This is achieved by various mechanisms incl uding the ability of the protein to adopt active and latent forms, its cell ular, localization, and control of p53 stability. The vast array of data on the atomic structure of the p53 protein, in conjuction with recent insight s into the biochemical mechanisms that fine-tune its activity open lip exci ting new avenues for the development of rational therapeutic approaches aim ing at restoring p53 function in a broad spectrum of human malignancies.