ArticleESMO open2025
Unraveling the complexity of HRD assessment in ovarian cancer by combining genomic and functional approaches: translational analyses of MITO16-MaNGO-OV-2 trial.
Article in ESMO open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- PD-L1 in Ovarian Cancer: Immune Evasion, Tumor-Intrinsic Signaling, and Chemoresistance.Cancer medicine · 2026Review
- Development and validation of a miRNA-based prognostic model for high-grade serous ovarian cancer: a retrospective cohort study.Lancet regional health. Americas · 2026Article
- CCDC6 Immunostaining in Conjunction with the Rad51 HRD Assay May Expand PARPi Treatment Eligibility in Patients with HGSOC.Cancer research communications · 2026Article
- Bevacizumab in ovarian cancer: Clinical data and predictive and prognostic biomarkers.Clinical and translational medicine · 2026Review
- Navigating PARP Inhibitor Resistance in Ovarian Cancer: Bridging Mechanistic Insights To Clinical Translation.Current treatment options in oncology · 2025Review
- Real-World Analysis of HRD Assay Variability in High-Grade Serous Ovarian Cancer: Impacts of BRCA1/2 Mutation Subtypes on HRD Assessment.Biomolecules · 2025Article
- Perspectives, Challenges, and Advances in Therapeutic Strategies for Gynecological Malignant Tumors.Biomedicines · 2025Article
- From Bench to Bedside in Emerging Therapies for Gynecological Malignancies: A Narrative Review.Cancer control : journal of the Moffitt Cancer CenterReview
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Authors and funding
25 authors.
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Abstract
backgroundOvarian cancer (OvC) constitutes significant management challenges primarily due to its late-stage diagnosis and the development of resistance to chemotherapy. The standard treatment regimen typically includes carboplatin and paclitaxel, with the addition of poly (ADP-ribose) polymerase inhibitors for patients with high-grade serous ovarian cancer (HGSOC) harboring BRCA1/2 mutations. However, the variability in treatment responses suggests the need to investigate factors beyond BRCA1/2 mutations, such as DNA repair mechanisms and epigenetic alterations. Notably, homologous recombination repair deficiency (HRD) is observed in an additional 20% of HGSOC cases, indicating a broader spectrum of DNA repair defects. Existing commercial HRD assays have certain limitations, prompting a global effort to develop new genomic and functional tests through academic research. MATERIALS AND
methodsThis study investigates, in the 187 high-grade serous and endometrioid tumors from the MITO16/MaNGO-OV-2 trial, academic HRD genomic tests in conjunction with a RAD51 immunofluorescence assay to assess functional activation of HRD. Additionally, the study incorporates analysis of microRNA-506 (miR-506) expression as a putative epigenetic effector.
resultsThe RAD51 test identified HRD in 73% of the samples and genomic HRD testing in 57%, with HRD identified in 45% of samples by both tests. The significant discrepancy between the two assays emphasizes the need to refine tumor classification for HRD. A three-group genomic classification unveiled superior progression-free survival (PFS) in high- and mild-HRD tumors compared with negative-HRD tumors. High concordance between RAD51 and genomic testing in high-HRD tumors suggests a subset of 'super-HRD' tumors exhibiting superior PFS. High expression of miR-506 may be used to further refine HRD status.
conclusionsThe study underscores the complexities of HRD assessment and advocates for a combined genomic and functional approach to enhance predictive accuracy in OvC treatment responses.
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