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

oleh: Justin Zonneville, Moyi Wang, Mohammed M. Alruwaili, Brandon Smith, Megan Melnick, Kevin H. Eng, Thomas Melendy, Ben Ho Park, Renuka Iyer, Christos Fountzilas, Andrei V. Bakin

Format: Article
Diterbitkan: Nature Portfolio 2021-07-01

Deskripsi

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.