Making the best of PARP inhibitors in ovarian cancer.
Drugs that inhibit the enzyme poly(ADP-ribose)polymerase (PARP) are showing considerable promise for the treatment of cancers that have mutations in the BRCA1 or BRCA2 tumor suppressors. This therapeutic approach exploits a synthetic lethal strategy to target the specific DNA repair pathway in these tumors. High-grade ovarian cancers have a generally poor prognosis, and accumulating evidence suggests that mutations in BRCA1 or BRCA2, or silencing of BRCA1 by promoter methylation, may be common in this disease. Here, we consider how the potential benefit of PARP inhibitors might be maximized in ovarian cancer. We suggest that it will be crucial to explore novel therapeutic trial strategies and drug combinations, and incorporate robust biomarkers predictive of response if these drugs are to reach their full potential.
Banerjee
Susana
S
The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK.
Kaye
Stan B
SB
Ashworth
Alan
A
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D019175:DNA Methylation; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011379:Prognosis; D042461:Vascular Endothelial Growth Factor A
D000970:Antineoplastic Agents; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D011065:Poly(ADP-ribose) Polymerases