TP53 tumour suppressor gene: clues to molecular carcinogenesis and cancer therapy.

The tumour suppressor gene product TP53 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. TP53 is functionally inactivated by mutational, viral and cellular mechanisms in the majority of human cancers. Analysis of the spectrum of TP53 mutations provides clues to the aetiology and molecular pathogenesis of cancer. Recent insight into the TP53 mediated biochemical pathways of cell cycle arrest and apoptosis has provided further understanding of the mechanisms related to TP53 mediated tumour suppression. This in turn may provide the potential molecular targets for the development of rational multimodality cancer therapy, including chemotherapy, immunotherapy and gene therapy strategies. The convergence of previously parallel lines of basic, clinical and epidemiological investigation may provide an opportunity for the rapid transfer of research findings from the laboratory to the clinic.