ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Functional Homologous Recombination Assay on FFPE Specimens of Advanced High-Grade Serous Ovarian Cancer Predicts Clinical Outcomes.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 26 citations in OpenAlex.
- Platinum Rechallenge in Platinum-Resistant Ovarian Cancer: Clinical Outcomes and the Impact of BRCA Status.Cancers · 2026Article
- Ex Vivo Immuno-Oncology Platform Reveals Spatial T-cell Infiltration Patterns Linked to ATR Inhibition Responses in High-Grade Serous Ovarian Cancer.Cancer immunology research · 2026Article
- Clinical application of PARP inhibitors and emerging strategies to overcome resistance: a pan-cancer perspective.Biomarker research · 2026Review
- Emerging Role of ctDNA Fragmentomics and Epigenetic Signatures in the Early Detection, Minimal Residual Disease Assessment, and Precision Monitoring of Renal Cell Carcinoma.Journal of cellular and molecular medicine · 2026Review
- Precision oncology in gynecologic cancers: molecular taxonomy, biomarker-guided therapeutics, and the challenge of therapeutic resistance.Frontiers in oncology · 2026Review
- Automated machine learning profiling with MAP-HR for quantifying homologous recombination foci in patient samples.NAR cancer · 2025Article
- Phospho-RPA2 predicts response to platinum and PARP inhibitors in homologous recombination-proficient ovarian cancer.The Journal of clinical investigation · 2025Article
- DNA damage response inhibitors in cancer therapy: lessons from the past, current status and future implications.Nature reviews. Drug discovery · 2025Review
- Chemotherapy induces myeloid-driven spatially confined T cell exhaustion in ovarian cancer.Cancer cell · 2024Article
- Prediction of homologous recombination deficiency from routine histology with attention-based multiple instance learning in nine different tumor types.BMC biology · 2024Article
- Prevalence of Homologous Recombination Deficiency Among Patients With Germline RAD51C/D Breast or Ovarian Cancer.JAMA network open · 2024Article
- Chemotherapy induces myeloid-driven spatial T-cell exhaustion in ovarian cancer.bioRxiv : the preprint server for biology · 2024Article
- Combining Homologous Recombination-Deficient Testing and Functional RAD51 Analysis Enhances the Prediction of Poly(ADP-Ribose) Polymerase Inhibitor Sensitivity.JCO precision oncology · 2024Article
- RAD51 as an immunohistochemistry-based marker of poly(ADP-ribose) polymerase inhibitor resistance in ovarian cancer.Frontiers in oncology · 2024Article
- Current HRD assays in ovarian cancer: differences, pitfalls, limitations, and novel approaches.Frontiers in oncology · 2024Review
- Review
- Diagnostic Laparoscopy for Advanced Ovarian, Fallopian Tube, and Peritoneal Cancers: A Retrospective Study.Gynecology and minimally invasive therapyArticle
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22 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
purposeDeficiency in homologous recombination (HR) repair of DNA damage is characteristic of many high-grade serous ovarian cancers (HGSC). It is imperative to identify patients with homologous recombination-deficient (HRD) tumors as they are most likely to benefit from platinum-based chemotherapy and PARP inhibitors (PARPi). Existing methods measure historical, not necessarily current HRD and/or require high tumor cell content, which is not achievable for many patients. We set out to develop a clinically feasible assay for identifying functionally HRD tumors that can predict clinical outcomes. EXPERIMENTAL
designWe quantified RAD51, a key HR protein, in immunostained formalin-fixed, paraffin-embedded (FFPE) tumor samples obtained from chemotherapy-naïve and neoadjuvant chemotherapy (NACT)-treated HGSC patients. We defined cutoffs for functional HRD separately for these sample types, classified the patients accordingly as HRD or HR-proficient, and analyzed correlations with clinical outcomes. From the same specimens, genomics-based HRD estimates (HR gene mutations, genomic signatures, and genomic scars) were also determined, and compared with functional HR (fHR) status.
resultsfHR status significantly predicted several clinical outcomes, including progression-free survival (PFS) and overall survival (OS), when determined from chemo-naïve (PFS, P < 0.0001; OS, P < 0.0001) as well as NACT-treated (PFS, P < 0.0001; OS, P = 0.0033) tumor specimens. The fHR test also identified as HRD those PARPi-at-recurrence-treated patients with longer OS (P = 0.0188).
conclusionsWe developed an fHR assay performed on routine FFPE specimens, obtained from either chemo-naïve or NACT-treated HGSC patients, that can significantly predict real-world platinum-based chemotherapy and PARPi response. See related commentary by Garg and Oza, p. 2957.
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