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The p53 tumor suppressor network in cancer and the therapeutic modulation of cell death

  • Cell Death and Disease
  • Published:
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Abstract

The molecular subversion of cell death is acknowledged as a principal contributor to the development and progression of cancer. The p53 tumor suppressor protein is among the most commonly altered proteins in human cancer. The p53 protein mediates critical functions within cells including the response to genotoxic stress, differentiation, senescence, and cell death. Loss of p53 function can result in enhanced rates of cell proliferation, resistance to cell death stimuli, genomic instability, and metastasis. The community of cancer scientists is now in possession of a vast repository of information regarding the frequency, specific mechanisms, and clinical context of cell death deregulation in cancer. This information has enabled the design of therapeutic agents to target proteins, including p53. The feasibility and impact of targeting cell death signaling proteins has been established in preclinical models of human cancer. The appropriate application of these targeted agents is now being established in clinical trials.

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Acknowledgments

This work was supported by The Mehta Family Foundation and NCI UO1 CA105345. NP is supported by the Department of Defense PC074107 and a Sowell-Huggins Predoctoral Fellowship. TJM is the recipient of the Sowell-Huggins Professorship in Cancer Research.

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  1. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Box 89, Houston, TX, 77030, USA

    Nikhil S. Chari, Nicole L. Pinaire, Lynnelle Thorpe, L. Jeffrey Medeiros, Mark J. Routbort & Timothy J. McDonnell

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Correspondence to Timothy J. McDonnell.

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Chari, N.S., Pinaire, N.L., Thorpe, L. et al. The p53 tumor suppressor network in cancer and the therapeutic modulation of cell death. Apoptosis 14, 336–347 (2009). https://doi.org/10.1007/s10495-009-0327-9

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