Inhibiteurs de la PARP : des avancées significatives dans le traitement des cancers

Poly(ADP-ribosyl)ation is a post-translational modification of proteins catalyzed by poly(ADP-ribose) polymerases (PARPs). In response to genotoxic stress, PARP-1 senses DNA breaks and through the synthesis of poly(ADP-ribose) restores genome integrity by stimulating a base excision and single-strand break repair process. These properties highlight the innovative potency of PARP inhibitors to target cancer cells in their repair capacity. They open the way to promising therapeutic strategies aimed to combine PARP inhibitors with DNA-damaging chimio- or radiotherapy and as single agents for the treatment of BRCA mutation-associated tumors. The benefits to potential risks ratio of these approaches will be discussed.