When the guardian sleeps: Reactivation of the p53 pathway in cancer

Publication date: Available online 17 February 2017
Source:Mutation Research/Reviews in Mutation Research
Author(s): Olaf Merkel, Ninon Taylor, Nicole Prutsch, Philipp Staber, Richard Moriggl, Suzanne Turner, Lukas Kenner
Half of all cancers carry loss of function mutations in the TP53 gene whereas in the other half, wild-type p53 protein is deactivated by other means. Hence, restoration of wild-type p53 function is of universal therapeutic importance for a multitude of cancers.In this review, we describe current therapeutic approaches targeting p53 and its two main antagonists MDM2 and MDM4, which lead to activation of the former and inhibition of the latter. These approaches include small molecule and peptidic inhibitors of MDM2 and MDM4 as well as compounds that act directly on p53; we also discuss gene therapy and vaccination strategies. It is clear that the mode of p53 inactivation in different cancers is diverse requiring a personalized approach for p53 associated treatment options.



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