Comment: Progress in PARP inhibitors beyond BRCA mutant recurrent ovarian cancer? - The Lancet Oncology Ovarian Cancer and Us OVARIAN CANCER and US Ovarian Cancer and Us

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Friday, December 02, 2016

Comment: Progress in PARP inhibitors beyond BRCA mutant recurrent ovarian cancer? - The Lancet Oncology

Progress in PARP inhibitors beyond BRCA mutant recurrent ovarian cancer? - The Lancet Oncology
 (not open access)
Up to half of newly diagnosed patients with high-grade serous ovarian cancer have a deficit in the homologous recombination system, which repairs double-strand breaks in DNA. Mutations in BRCA1 or BRCA2, which occur in roughly 20% of patients (16% germline and 4% somatic), are the most common cause of homologous recombination deficiency.1 Patients with BRCA mutations have longer overall survival than do patients without such mutations, and their tumours are extremely sensitive to platinum-based chemotherapy and poly (ADP-ribose) polymerase (PARP) inhibitors.



  1. Nielsen, FC, van Overeem Hansen, T, and Sørensen, CS. Hereditary breast and ovarian cancer: new genes in confined pathways. Nat Rev Cancer. 2016; 16: 599–612
  2. Konstantinopoulos, PA, Ceccaldi, R, Shapiro, GI, and D'Andrea, AD. Homologous recombination deficiency: exploiting the fundamental vulnerability of ovarian cancer. Cancer Discov. 2015; 5: 1137–1154
  3. Ledermann, J, Harter, P, Gourley, C et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol. 2014; 15: 852–861
  4. Kaufman, B, Shapira-Frommer, R, Schmutzler, RK et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015; 33: 244–250
  5. Gelmon, KA, Tischkowitz, M, Mackay, H et al. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol. 2011; 12: 852–861
  6. Abkevich, V, Timms, KM, Hennessy, BT et al. Patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer. Br J Cancer. 2012; 107: 1776–1782
  7. Watkins, JA, Irshad, S, Grigoriadis, A, and Tutt, AN. Genomic scars as biomarkers of homologous recombination deficiency and drug response in breast and ovarian cancers. Breast Cancer Res. 2014; 16: 211
  8. Swisher, EM, Lin, KK, Oza, AM et al. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncology. 2016; (published online Nov 28.)
  9. Coleman, RL, Swisher, EM, and Oza, AM. Refinement of prespecified cutoff for genomic loss of heterozygosity in ARIEL2 part 1: a phase II study of rucaparib in patients (pts) with high grade ovarian carcinoma. Proc Am Soc Clin Oncol. 2016; 34 (abstr 5540.)
  10. Mirza, MR, Monk, BJ, Herrstedt, J et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016; (published online Oct 7.)


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