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Review
. 2017 Apr;9(4):253-267.
doi: 10.1177/1758834016687254. Epub 2017 Feb 3.

PARP inhibitors in ovarian cancer: evidence, experience and clinical potential

Tarra Evans  1 , Ursula Matulonis  2
Affiliations
Review

PARP inhibitors in ovarian cancer: evidence, experience and clinical potential

Tarra Evans et al. Ther Adv Med Oncol. 2017 Apr.

Abstract

Inhibitors of poly(ADP-ribose) polymerase (PARP) are considered one of the most active and exciting new therapies for the treatment of ovarian cancer. The anticancer activity of PARP inhibitors is based on the DNA repair vulnerability of many ovarian cancer cells, and multiple mechanisms of action of PARP inhibitors have been identified. As single agents, PARP inhibitors have demonstrated their greatest activity in ovarian cancer cells that harbor mutations in BRCA genes. Additionally, recent phase III studies have shown that single-agent PARP inhibitor activity extends beyond BRCA-related cancers and can benefit patients with ovarian cancers that do not have known BRCA mutations, especially when clinical characteristics such as platinum sensitivity and high-grade serous histology are present. PARP inhibitors have also been combined with chemotherapy, however, overlapping myelosuppression observed with PARP inhibitor and chemotherapy combinations has hampered development of these combinations. Contrariwise, PARP inhibitor and biologic agent combinations, specifically antiangiogenic agents, appear well tolerated and show promising activity in both BRCA mutated (BRCAm) and BRCA wild-type (BRCAwt) cancers. Currently, multiple clinical trials are underway examining the antitumor activity of PARP inhibitor combination therapy.

Keywords: BRCA mutations; PARP inhibitors; ovarian cancer; targeted therapy.

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Conflict of interest statement

Conflict of interest statement: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Matulonis reports the following conflicts of interest: Clovis: advisory board Astrazeneca: advisory board and consulting Genentech Roche: advisory board Immunogen: consulting Eli Lilly: advisory board.

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