Genomics of ovarian cancers and the potential of precision medicine
- Author(s)
- Jarratt, A; Polidano, J; Scott, CL; Barker, HE;
- Journal Title
- Therapeutic Advances in Medical Oncology
- Publication Type
- Review
- Abstract
- Epithelial ovarian cancer (OC) comprises molecularly distinct disease types, with high-grade serous ovarian cancer (HGSOC) accounting for ~75% of OC diagnoses; ovarian clear cell carcinoma (OCCC) and endometrioid ovarian carcinoma (EnOC) at ~10% each; mucinous ovarian carcinoma (MOC) and low-grade serous ovarian carcinoma (LGSOC) at ⩽5% each; and ovarian carcinosarcoma (OCS), the rarest type of OC at 1%-4% of OC diagnoses. LGSOC has the best prognosis, followed by EnOC, MOC and OCCC, with HGSOC then OCS being the most aggressive. For all types of OC, diagnosis at the advanced-stage results in dramatically reduced survival. Initial treatment consists of debulking surgery and platinum-based chemotherapy, usually in combination with a taxane; however, response rates vary depending on the OC type. Treatments specific to the OC type may improve treatment outcomes. For HGSOC, poly(ADP-ribose) polymerase inhibitor (PARPi) therapy has improved survival for women with DNA homologous recombination repair (HRR) defects; however, acquired resistance remains an issue and more effective treatments are needed. Next-generation sequencing of distinct types of OC has revealed the complexity of genetic variants and larger-scale genomic and epigenomic alterations harboured, including proven and putative biomarkers of drug response. A predominance of distinct gene classes is altered in specific OC types: HRR genes (e.g. BRCA1 and BRCA2) in HGSOC; ARID1A and PIK3CA in OCCC; PIK3CA and KRAS in EnOC; CDKN2A and KRAS in MOC and MAPK pathway genes (e.g. BRAF and KRAS) in LGSOC. Generating evidence for effective drug combination therapies targeting relevant aberrations in each OC type is urgently needed. The effects of long-term drug treatment on OC genomes, acquired drug-resistance and OC relapse require clarification, especially in women with HGSOC with acquired resistance to PARPi. This article provides an overview of the main types of OC and their genomic profiles. It highlights recent encouraging clinical trials, with an emphasis on the future of genomically-targeted combination therapies, for both first-line and subsequent treatment of OC. We focus on PARPi combinations for HGSOC, MAPK pathway inhibitors for LGSOC, cell cycle checkpoint inhibitors for OC with CCNE1 amplification, the potential of immune checkpoint inhibitors in OCCC and encouraging, as yet preliminary, responses for antibody-drug conjugate-based therapy. Thus, OC type-specific genomic susceptibilities provide direction for personalised therapy in OC.; Investigating the potential of matching drugs to specific changes in the DNA in ovarian cancers Ovarian cancer (OC) can be divided into distinct disease types based on the cell type from which the cancer originated, with high-grade serous ovarian cancer being the most prevalent OC type. Each type of OC can be further classified by changes in the DNA which affect specific genes. Treatment options are increasing as a result of the number of drugs in clinical trials shown to have efficacy in matching these DNA changes. Changes in the DNA may affect cancer cell growth and survival, DNA repair, or interaction of the cancer cells with the immune system. Finding effective drug combinations to target these changes is essential, to most effectively treat patients. In addition, understanding how long-term drug treatment may lead to drug resistance and OC relapse is crucial. In this review, we describe the most frequent DNA or protein changes observed in the different types of OC and discuss different therapies currently being investigated to target these changes. We focus on PARP inhibitors, MAPK pathway inhibitors, cell cycle checkpoint inhibitors, immune checkpoint inhibitors, and antibody-drug conjugate (ADC)-based therapies for specific OC types depending on genomic susceptibilities.; eng
- Publisher
- Sage
- Keywords
- clinical trials; epithelial ovarian cancer; homologous recombination deficiency (HRD); molecular profiling; molecular therapeutics; targeted therapy
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1177/17588359251396651
- Open Access at Publisher's Site
https://doi.org/10.1177/17588359251396651- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2026-01-13 04:29:44
Last Modified: 2026-01-13 04:29:53