Abstract
Reinstatement of the p53 tumor suppressor function in cancers by small molecules is a promising strategy to combat cancer. In this chapter, we focus on the concept of targeting wild-type p53 and different approaches that have been explored to activate wild-type p53 in tumors. We discuss the emerging notion that small molecules targeting p53 can induce conformational changes that may lead to reactivation of both mutant and wild-type p53. Given that p53 participates in a bewildering diversity of biological processes and that small molecules might have more than one target in a cell, dissecting tumor cell responses to different p53-activating compounds presents a tremendous challenge. We discuss cellular factors that have been shown to modulate the outcome of p53 induction by different compounds. Elucidation of the mechanisms governing the p53 response upon different activating stimuli is of utmost importance for the efficient implementation of p53-targeting treatments into clinical practice.
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Grinkevich, V.V., Warnecke, A., Selivanova, G. (2013). p53-Reactivating Molecules as Research Tools and Anticancer Drugs. In: Hainaut, P., Olivier, M., Wiman, K. (eds) p53 in the Clinics. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3676-8_13
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