If p53 can't do it, ask p73

Abstract

Promoting p53's function, without causing damage to the genome is widely accepted as a way to improve treatment of cancer. In the case of tumours where the p53 gene is not mutated or absent, there have been important advances in the recent past. Small molecules that, like the nutlins discovered by Luo Vassilev and colleagues,1 efficiently activate wild type p53 by inhibiting the function of p53's major negative regulator mdm2 and show promising results in preclinical models as single agents or in combination with classic chemotherapeutics.2 Finding compounds that instead of binding to mdm2, interact with p53 and prevent its degradation whilst still allowing its function, is also an approach under investigation.3 Restoring p53 effects in tumours that contain point mutations in the p53 gene is in some ways a bigger challenge. One possible way to achieve this is through peptides or small molecules that directly interact with mutant p53.4,5 Because, unlike wild type p53, mutant p53 is expressed at very high l...