Trial reportGynecologic oncology2019
53BP1 as a potential predictor of response in PARP inhibitor-treated homologous recombination-deficient ovarian cancer.
Trial report in Gynecologic oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Drug resistance biomarkers in ovarian cancer: a bibliometric study from 2017 to 2022.Frontiers in oncology · 2024Pooled it
- NCI10066: a Phase 1/2 study of olaparib in combination with ramucirumab in previously treated metastatic gastric and gastroesophageal junction adenocarcinoma.British journal of cancer · 2024Trial
- Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2).Nature communications · 2021Trial
- BCLXSignal transduction and targeted therapy · 2026Article
- Mechanisms and disease relevance of DNA break repair pathway choice.Nature reviews. Molecular cell biology · 2026Review
- Sensitizing Colorectal Cancer to PARP Inhibitors: Biomarkers, Mechanisms, and Combination Strategies.International journal of molecular sciences · 2026Review
- Codon specific readthrough as a mechanism of BRCA2 restoration in acquired PARP inhibitor and chemotherapy resistance.Nucleic acids research · 2025Article
- DNA repair and the contribution to chemotherapy resistance.Genome medicine · 2025Review
- Suppression of ADP-ribosylation reversal triggers cell vulnerability to alkylating agents.Neoplasia (New York, N.Y.) · 2025Article
- Star wars against leukemia: attacking the clones.Leukemia · 2024Review
- Poly (ADP-ribose) polymerase inhibitor therapy and mechanisms of resistance in epithelial ovarian cancer.Frontiers in oncology · 2024Review
- BRCA1/2 alterations and reversion mutations in the area of PARP inhibitors in high grade ovarian cancer: state of the art and forthcoming challenges.Frontiers in oncology · 2024Review
- ZNF432 stimulates PARylation and inhibits DNA resection to balance PARPi sensitivity and resistance.Nucleic acids research · 2023Article
- UGDH promotes tumor-initiating cells and a fibroinflammatory tumor microenvironment in ovarian cancer.Journal of experimental & clinical cancer research : CR · 2023Article
- Adenosine receptor A2b confers ovarian cancer survival and PARP inhibitor resistance through IL-6-STAT3 signalling.Journal of cellular and molecular medicine · 2023Article
- RAD51 Foci as a Biomarker Predictive of Platinum Chemotherapy Response in Ovarian Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- The presence of clear cell glands around the ovarian endometrioid cyst has an association with clear cell carcinoma.Virchows Archiv : an international journal of pathology · 2023Article
- PARP inhibitors, use early in the first-line maintenance therapy setting but with caution.Annals of translational medicine · 2023Article
- Olaparib-ResistantCells · 2023Article
- Targeting the DNA damage response for cancer therapy.Biochemical Society transactions · 2023Article
Corrections and comments
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Authors and funding
22 authors at 8 institutions in 2 countries.
Funding
Abstract
objectivePoly(ADP-ribose) polymerase (PARP) inhibitors have shown substantial activity in homologous recombination- (HR-) deficient ovarian cancer and are undergoing testing in other HR-deficient tumors. For reasons that are incompletely understood, not all patients with HR-deficient cancers respond to these agents. Preclinical studies have demonstrated that changes in alternative DNA repair pathways affect PARP inhibitor (PARPi) sensitivity in ovarian cancer models. This has not previously been assessed in the clinical setting.
methodsClonogenic and plasmid-based HR repair assays were performed to compare BRCA1-mutant COV362 ovarian cancer cells with or without 53BP1 gene deletion. Archival biopsies from ovarian cancer patients in the phase I, open-label clinical trial of PARPi ABT-767 were stained for PARP1, RAD51, 53BP1 and multiple components of the nonhomologous end-joining (NHEJ) DNA repair pathway. Modified histochemistry- (H-) scores were determined for each repair protein in each sample. HRD score was determined from tumor DNA.
results53BP1 deletion increased HR in BRCA1-mutant COV362 cells and decreased PARPi sensitivity in vitro. In 36 women with relapsed ovarian cancer, responses to the PARPi ABT-767 were observed exclusively in cancers with HR deficiency. In this subset, 7 of 18 patients (39%) had objective responses. The actual HRD score did not further correlate with change from baseline tumor volume (r = 0.050; p = 0.87). However, in the HR-deficient subset, decreased 53BP1 H-score was associated with decreased antitumor efficacy of ABT-767 (r = -0.69, p = 0.004).
conclusionDifferences in complementary repair pathways, particularly 53BP1, correlate with PARPi response of HR-deficient ovarian cancers.
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