Poly(ADP-ribose) polymerase inhibitor development: are we in the right direction?

Excerpt

Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear DNA-binding enzyme activated by DNA strand breaks and has a key role in the signalling of DNA single-strand breaks as part of the repair process. In anti-cancer therapy, many agents cause DNA damage as their mechanism of cytotoxicity, and repair of damage is a cause of tumour resistance. Additionally in tumours where double-strand break repair is defective (for example in BRCA-related cancers) PARP inhibitors have potential single-agent activity. Thus, PARP-1 was identified as a potential therapeutic target for cancer treatment and PARP inhibitors have entered the clinic both in combination with cytotoxic chemotherapy, as single agents in DNA repair deficient tumours, and more recently in combination with radiotherapy. …