~50% of high-grade serous ovarian cancers have genetic or epigenetic defects in HRR pathways, which results in HRD [1]. The most commonly affected genes in serous or non-serous ovarian cancers are BRCA1 and BRCA2, with contributions from other HRR genes such as RAD51C, RAD51D, ATM, BARD1, PALB2 and BRIP1 being responsible for ~10% of HRD cases [2].
There is a strong association between HRD and ovarian cancer platinum-sensitivity, which likely explains why platinum-sensitivity has been successfully used as a clinical tool for patient selection for PARP inhibitor therapy [2-4].
Further information on the clinical activity of PARP inhibitors in ovarian cancer can be found by clicking on each topic below.
References
- Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature 2011; 474: 609-615.
- Pennington KP, Walsh T, Harrell MI et al. Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas. Clin Cancer Res 2014; 20: 764-775.
- Fong PC, Yap TA, Boss DS et al. Poly(ADP)-ribose polymerase inhibition: frequent durable responses in BRCA carrier ovarian cancer correlating with platinum-free interval. J Clin Oncol 2010; 28: 2512-2519.
- Gourley C, Balmana J, Ledermann JA et al. Moving from PARP Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy. J Clin Oncol 2019; doi: 10.1200/JCO.1218.02050. [Epub ahead of print].