A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy

Chemotherapy and radiation therapy for cancer often have severe side effect s that limit their efficacy. Because these effects are in part determined b y p53-mediated apoptosis, temporary suppression of p53 has been suggested a s a therapeutic strategy to prevent damage of normal tissues during treatme nt of p53-deficient tumors. To test this possibility, a small molecule was isolated for its ability to reversibly block p53-dependent transcriptional activation and apoptosis. This compound, pifithrin-alpha, protected mice fr om the Lethal genotoxic stress associated with anticancer treatment without promoting the formation of tumors. Thus, inhibitors of p53 may be useful d regs for reducing the side effects of cancer therapy and other types of str ess associated with p53 induction.