PARP inhibitors and epithelial ovarian cancer: an approach to targeted chemotherapy and personalised medicine.
Poly-ADP ribose polymerase (PARP) inhibitors have emerged as exciting new chemotherapy options for women with ovarian cancer. They exploit a mechanism known as synthetic lethality by targeting specific DNA repair pathways. Recent Phase II clinical trials have shown great promise in treating women with hereditary breast and ovarian cancers associated with BRCA1/2 mutations. Most importantly, they appear to be associated with only minimal adverse effects. However, up to 50-60% of epithelial ovarian cancers are defective in their ability to repair DNA damage using homologous recombination and could potentially benefit from these agents providing a scope both for targeted chemotherapy and personalised medicine. Ongoing clinical trials are investigating the potential benefit of this agent in treatment of high-grade serous epithelial ovarian cancers and in platinum-resistant disease.
Northern Gynaecological Oncology Centre, Queen Elizabeth Hospital, Gateshead, UK.
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Mukhopadhyay
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Curtin
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Plummer
R J
RJ
Edmondson
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077216:Carcinoma, Ovarian Epithelial; D018890:Chemoprevention; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005544:Forecasting; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D009154:Mutation / Q000235:genetics; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D057285:Precision Medicine
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors