p53 in the clinics : prognosis, prediction, therapy

Orateur : Pierre HAINAUT (International Prevention Research Institute, Lyon)

Initially ignored by many researchers as an outsider molecule of minor importance in carcinogenesis, p53 took over 10 years to rise to the status of “guardian of the genome (1992)” and “molecule of the year” (1993). Yet, despite all the hype of the 1990s, the path from molecular discoveries to clinical application has been frustratingly long and winding for p53. It is only in recent years that breakthroughs have started to accumulate, opening doors to applications of the huge amount of knowledge accumulated on p53 into clinical practice. If p53 is not yet part of the everyday cancer management, with the rapid diversification of translational research on p53 detection and treatment, the road towards major clinical applications is now rapidly clearing up. Discovered in 1979, the p53 protein has now reached the full maturity age of 33—which does not necessarily mean that it is ready to deliver healing miracles in public health care. The role of p53 as a regulator of cell cycle checkpoints and cell death in response to multiple cellular stresses is definitively established as well as experimental models for studying p53, knowledge on the prognostic and predictive value of tumor-associated p53 mutations and emerging therapeutic strategies for restoring p53 function in tumors. The p53 field has developed at an ever-increasing pace and p53 researchers have uncovered novel and entirely unexpected functions and aspects of p53. There has been substantial progress on the significance of the genetic diversity of p53 and on mutations as biomarkers in molecular pathology. Research on p53-based therapy has intensified dramatically with the development of several drugs that target the p53 pathway. Thus, there have been considerable advances on the potential applications of p53 in the clinic. The goal of this talk is to capture these developments as the field moves into a next phase with strong emphasis on translational research.

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