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Therapeutic Strategies Based on Pharmacological Modulation of p53 Pathway

  • Chapter
The p53 Tumor Suppressor Pathway and Cancer

Part of the book series: Protein Reviews ((PRON,volume 2))

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Abstract

p53 plays a dual role in cancer treatment being, on one hand, a major cancer preventive factor, which can kill or sensitize tumors to radio- and chemotherapy and, on the other hand, a determinant of cancer treatment side effects by inducing apoptosis in normal tissues during cancer therapy. This dualism defines two major therapeutic applications targeting p53: p53 activation to reduce viability of tumor cells and p53 inhibition to increase the viability of normal cells thereby reducing treatment side effects. Prospective new anticancer agents are being developed that recover p53 function in tumor cells by disrupting its interactions with natural inhibitors, such as MDM2 or E6, or restore wild-type conformation of mutant p53. In parallel, p53 inhibitory strategy is being developed to protect normal tissues from chemo- and radiotherapy and to treat other pathologies associated with stress-mediated activation of p53.

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  1. Department of Molecular Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA

    Andrei V. Gudkov

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  1. St. Jude Children’s Research Hospital, Memphis, Tennessee

    Gerard P. Zambetti

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Gudkov, A.V. (2005). Therapeutic Strategies Based on Pharmacological Modulation of p53 Pathway. In: Zambetti, G.P. (eds) The p53 Tumor Suppressor Pathway and Cancer. Protein Reviews, vol 2. Springer, Boston, MA. https://doi.org/10.1007/0-387-30127-5_10

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