Targeting poly(ADP-ribose) polymerase: a two-armed strategy for cancer therapy.
The DNA repair pathways are protective of the host genome in normal cells; however, in cancer cells, these pathways may be disrupted and predispose to tumorigenesis or their activity may overcome the potentially cytotoxic damage caused by anticancer agents and be a mechanism of resistance. Poly(ADP-ribose) polymerase inhibitors, which block base excision repair of single-strand breaks, have entered the clinic in the last few years. This article discusses the interactions between the pathways of single- and double-strand break repair, which explain the two clinical development strategies for this class of drugs.
Plummer
Elizabeth Ruth
ER
Northern Institute for Cancer Research, Newcastle University, United Kingdom. e.r.plummer@ncl.ac.uk
Calvert
Hilary
H
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001665:Binding Sites; D004249:DNA Damage; D004260:DNA Repair; D016678:Genome; D015894:Genome, Human; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*
D000970:Antineoplastic Agents; D011065:Poly(ADP-ribose) Polymerases