Homologous recombination deficiency in ovarian cancer: a review of its epidemiology and management

Abstract

Ovarian cancer patients with homologous recombination deficiencies exhibit specific clinical behaviors, and improved responses to treatments, such as platinum-based chemotherapy and poly (ADP-ribose) polymerase (PARP) inhibitors, have been observed. Germline mutations in the BRCA 1/2 genes are the most well-known mechanisms of homologous recombination deficiency. However, other mechanisms, such as germline and somatic mutations in other homologous recombination genes and epigenetic modifications, have also been implicated in homologous recombination deficiency. The epidemiology and implications of these other mechanisms need to be better understood to improve the treatment strategies for these patients. Furthermore, an evaluation of various diagnostic tests to investigate homologous recombination deficiency is essential. Comprehension of the role of homologous recombination deficiency in ovarian cancer also allows the development of therapeutic combinations that can improve the efficacy of treatment. In this review, we discuss the epidemiology and management of homologous recombination deficiency in ovarian cancer patients.

Identification of Potential Biomarkers in Association With Progression and Prognosis in Epithelial Ovarian Cancer by Integrated Bioinformatics Analysis

“…Interestingly, the study by Ren JG et al found that citrate suppressed tumor growth through inhibition of glycolysis, the TCA cycle and the insulin-like growth factor-1 receptor pathway (Ren et al, 2017). Homologous recombination deficiency was closely related to ovarian cancer and breast cancer (Zhao et al, 2017; Da et al, 2018). These examples show that the results of GESA analysis can be used as a reference for oncogenesis studies to some extent.…”

Overcoming immunotherapy resistance in non-small cell lung cancer (NSCLC) - novel approaches and future outlook

“…Double-strand DNA breaks are repaired by homologous recombination (HR). The germline BRCA1/2 genes are involved in HR mechanism and their mutation may lead to HR deficiency (HRD) [ 95 ]. HRD alone does not always induce apoptosis as other repair mechanisms can prohibit accumulation of damaged DNA.…”

“…HRD alone does not always induce apoptosis as other repair mechanisms can prohibit accumulation of damaged DNA. However, impairing two DDR mechanisms by adding PARPi to HR-deficient cells can lead to cell death (synthetic lethality) [ 95 ].…”

Advances in epithelial ovarian cancer

“…Nine per cent of ovarian cancers have a somatic (non-inherited, tumour-specific) BRCA mutation, and 18% have other HRD mutations, which makes both groups respond to molecular targeted therapies that inhibit the enzyme PARP. 24 Accordingly, PARPis are particularly active in gBRCA mutation carriers and also show activity in women with somatic BRCA (sBRCA) mutations and HRDs, but at a lower rate. Olaparib is one PARPi that, when used as oral maintenance treatment in gBRCA mutation carriers, has shown 60% DFS at three years, compared with 27% in controls.…”