PARP inhibitors – a new direction in the treatment of breast and ovarian cancer

Abstract

Ovarian cancer, like breast cancer, may either develop spontaneously or as a result of a family history. BRCA1 and BRCA2 mutations significantly increase the risk of both cancers at all ages. It is estimated that 3–5% of women are BRCA mutation carriers. BRCA1 mutation carriers have a 65% risk of breast cancer and 39% risk of ovarian cancer. These risks are lower among BRCA2 mutation carriers, i.e. 45% and 11% for breast and ovarian cancer, respectively. In breast and ovarian cancer with BRCA mutations, blocking the function of poly(ADP-ribose) polymerase (PARP) enzymes, including PARP1 and PARP2, causes an accumulation of DNA damage that ultimately leads to cancer cell death. Based on this mechanism, PARP inhibitors have been used in the treatment of hereditary neoplasms, in which the proper functioning of DNA damage repair systems is disturbed. In clinical trials to date, PARP inhibitors significantly extended the progression-free survival in patients with confirmed BRCA mutations. Similar results have been obtained for patients without confirmed genetic background. Currently, PARP inhibitors are increasingly approved for use in the treatment of ovarian and breast cancer. From May 2021, the Ministry of Health has reimbursed maintenance therapy with PARP inhibitors in patients with known BRCA mutation status.