Selective therapeutic strategy for p53-deficient cancer by targeting dysregulation in DNA repair

Abstract

Zonneville et al. show that p53 mutant cancers express high levels of the Base Excision Repair (BER) pathway and that deoxyuridine analogues induce DNA damage in p53-mutant TNBC cells. They exploit this genetic liability for therapeutic purposes using a combination of fluorinated deoxyuridine analogues and PARP1 inhibitors to target the BER pathway, inducing cytotoxicity and suppressing tumor growth in mice.