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  • Title: Restoration of wild-type p53 function in human tumors: strategies for efficient cancer therapy.
    Author: Wiman KG.
    Journal: Adv Cancer Res; 2007; 97():321-38. PubMed ID: 17419952.
    Abstract:
    The p53 tumor suppressor gene is mutated in around 50% of all human tumors. Most mutations inactivate p53's specific DNA binding, resulting in failure to activate transcription of p53 target genes. As a consequence, mutant p53 is unable to trigger a p53-dependent biological response, that is cell cycle arrest and apoptosis. Many tumors express high levels of nonfunctional mutant p53. Several strategies for restoration of wild-type p53 function in tumors have been designed. Wild-type p53 reconstitution by adenovirus-mediated gene transfer has shown antitumor efficacy in clinical trials. Screening of chemical libraries has allowed identification of small molecules that reactivate mutant p53 and trigger mutant p53-dependent apoptosis. These novel strategies raise hopes for more efficient cancer therapy.
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