Understanding BRCAwt

The majority of women with recurrent ovarian cancer have BRCA wild-type tumors1

Preclinical studies suggest that higher concentrations of a PARP inhibitor may be needed to induce cell death in BRCAwt tumors3

BRCAwt cell lines are less sensitive to PARP inhibition. However, these cell lines respond to higher concentrations of PARP inhibitors, resulting in cancer cell death3

Beyond BRCA status

Understanding BRCA and other alterations in DNA repair pathways

  • PARP inhibitors exploit the tumor cell's inability to repair DNA5
  • Nearly 2/3 of tumors harbor some kind of DNA-repair deficiencies; however, standardized tests do not conclusively identify all patients with these deficiencies

BRCAwt patients have a narrow window of opportunity to benefit from a PARP inhibitor7-11

References: 1. Hollis RL, Churchman M, Gourley C. Distinct implications of different BRCA mutations: efficacy of cytotoxic chemotherapy, PARP inhibition and clinical outcome in ovarian cancer. Onco Targets Ther. 2017;10:2539-2551. 2. Bryant HE, Schultz N, Thomas HD, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434(7035):913-917. 3. Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434(7035):917-921. 4. Data on file. TESARO, Inc. 5. da Cunha Colombo Bonadio RR, Fogace RN, Miranda VC, Diz MDPE. Homologous recombination deficiency in ovarian cancer: a review of its epidemiology and management. Clinics (Sao Paulo). 2018;73(suppl 1):e450s. 6. Konstantinopoulos PA, Ceccaldi R, Shapiro GI, D’Andrea AD. Homologous recombination deficiency: exploiting the fundamental vulnerability of ovarian cancer. Cancer Discov. 2015;5(11):1137-1154 7. ZEJULA (niraparib) [package insert]. Waltham, MA: TESARO, Inc.; February 2019. 8. Avastin (bevacizumab) [package insert]. South San Francisco, CA: Genentech, Inc; May 2018. 9. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Ovarian Cancer including Fallopian Tube Cancer and Primary Peritoneal Cancer V.4.2017. © National Comprehensive Cancer Network, Inc. 2017 All rights reserved. Accessed January 16, 2018. To view the most recent and complete version of the guidelines, go online to NCCN.org. 10. Lynparza (olaparib) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; December 2018. 11. Rubraca (rucaparib) [package insert]. Boulder, CO: Clovis Oncology, Inc; April 2018.

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