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      Awakening guardian angels: drugging the p53 pathway.

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          Abstract

          Currently, around 11 million people are living with a tumour that contains an inactivating mutation of TP53 (the human gene that encodes p53) and another 11 million have tumours in which the p53 pathway is partially abrogated through the inactivation of other signalling or effector components. The p53 pathway is therefore a prime target for new cancer drug development, and several original approaches to drug discovery that could have wide applications to drug development are being used. In one approach, molecules that activate p53 by blocking protein-protein interactions with MDM2 are in early clinical development. Remarkable progress has also been made in the development of p53-binding molecules that can rescue the function of certain p53 mutants. Finally, cell-based assays are being used to discover compounds that exploit the p53 pathway by either seeking targets and compounds that show synthetic lethality with TP53 mutations or by looking for non-genotoxic activators of the p53 response.

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          Author and article information

          Journal
          Nat Rev Cancer
          Nature reviews. Cancer
          Springer Science and Business Media LLC
          1474-1768
          1474-175X
          Dec 2009
          : 9
          : 12
          Affiliations
          [1 ] p53 Laboratory (A-STAR), 8A Biomedical Grove, Immunos, Singapore 138648.
          Article
          nrc2763
          10.1038/nrc2763
          19935675
          21f4e690-f239-434c-b58d-f008fdefbd80
          History

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