The Emerging Role of PARP Inhibitors in the Treatment of Epithelial Ovarian Cancer.
Poly(ADP-ribose) polymerase-1 (PARP-1) is an important novel target in cancer therapy. This enzyme is essential in the repair of single-stranded breaks in DNA via the base excision repair pathway. Drugs which inhibit PARP are emerging as a promising new class of anticancer agents particularly effective against tumors which have lost homologous recombination (HR) through loss of functional BRCA1 and BRCA2. PARP inhibitors potentially represent a major breakthrough for patients with hereditary BRCA-associated cancers. Furthermore their role in sporadic epithelial ovarian cancer is emerging with identification of additional subpopulations of women who may benefit a priority. This paper will summarize the mechanism of action of PARP inhibition and its role in the treatment of BRCA1- and 2-associated cancers. We will then expand on the broader relevance and future directions for PARP inhibition in the clinical setting.
Gien
Lilian T
LT
Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada M5G 2M9.
Mackay
Helen J
HJ