p53 tumor-suppressor gene: clues to molecular carcinogenesis.

The tumor-suppressor gene product p53 is clearly a component in several biochemical pathways, including transcription, DNA repair, genomic stability, cell-cycle control and apoptosis, that are central to human carcinogenesis. The p53 is functionally inactivated by mutational, viral, and cellular mechanisms in the majority of human cancers. Analysis of the spectrum of p53 mutations provides clues to the etiology and molecular pathogenesis of cancer. Recent insight into the p53-mediated biochemical pathways of cell-cycle arrest and apoptosis has provided further understanding of the mechanisms related to p53-mediated tumor suppression. This insight in turn may provide the potential molecular targets for the development of rational multimodality cancer therapy, including chemo-, immuno-, and gene-therapeutic strategies. The convergence of previously parallel lines of basic, clinical, and epidemiologic investigation may provide an opportunity to transfer research findings rapidly from the laboratory to the clinic.