ArticleJournal of hematology & oncology2021
VEGF pathway inhibition potentiates PARP inhibitor efficacy in ovarian cancer independent of BRCA status.
Article in Journal of hematology & oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses 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
33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 58 citations in OpenAlex.
- Efficacy and safety of VEGF/VEGFR inhibitors for platinum-resistant ovarian cancer: a systematic review and meta-analysis of randomized controlled trials.BMC women's health · 2024Pooled it
- Efficacy and Safety of Olaparib Combined With Cediranib in the Treatment of Ovarian Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Technology in cancer research & treatmentPooled it
- Antitumor activity and structure-activity relationship of poly (ADP-ribose) polymerase (PARP)-based dual inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- Vascular Protection of Poly(ADP-ribose) Polymerase Inhibitors in the Combination Therapy With Vascular Endothelial Growth Factor Signaling Pathway Inhibitors.Reviews in cardiovascular medicine · 2026Review
- Impairment of oxidative metabolism compromises Rad51 recruitment and potentiates PARP inhibitor effectiveness in ovarian cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Chemotherapy-free combination strategies in recurrent platinum-resistant ovarian cancer: promise, evidence and perspectives.Translational cancer research · 2025Article
- Vascular endothelial generating factor pathway in ovarian cancer.Journal of ovarian research · 2025Review
- GX15-070 enhances niraparib efficacy in ovarian cancer by promoting a shift in Mcl1-mediated DNA repair pathway from HR to NHEJ.Journal of translational medicine · 2025Article
- Natural Metabolites as Modulators of Sensing and Signaling Mechanisms: Unlocking Anti-Ovarian Cancer Potential.Biomedicines · 2025Review
- Identification of parthanatos-related molecular subtypes and development of prognostic risk models in ovarian cancer based on multi-omics analysis.Journal of ovarian research · 2025Article
- 'Where is my gap': mechanisms underpinning PARP inhibitor sensitivity in cancer.Biochemical Society transactions · 2025Review
- FLT1 activation in cancer cells promotes PARP-inhibitor resistance in breast cancer.EMBO molecular medicine · 2024Article
- Effect of ubiquitin protease system on DNA damage response in prostate cancer (Review).Experimental and therapeutic medicine · 2024Review
- Homologous recombination proficient subtypes of high-grade serous ovarian cancer: treatment options for a poor prognosis group.Frontiers in oncology · 2024Review
- Progesterone Enhances Niraparib Efficacy in Ovarian Cancer by Promoting Palmitoleic-Acid-Mediated Ferroptosis.Research (Washington, D.C.) · 2024Article
- PSPC1 Inhibition Synergizes with Poly(ADP-ribose) Polymerase Inhibitors in a Preclinical Model of BRCA-Mutated Breast/Ovarian Cancer.International journal of molecular sciences · 2023Article
- PARP inhibitors: enhancing efficacy through rational combinations.British journal of cancer · 2023Review
- 3D-QSAR, molecular docking, and molecular dynamics analysis of dihydrodiazaindolone derivatives as PARP-1 inhibitors.Journal of molecular modeling · 2023Article
- The PARP1 Inhibitor AZD5305 Impairs Ovarian Adenocarcinoma Progression and Visceral Metastases in Patient-derived Xenografts Alone and in Combination with Carboplatin.Cancer research communications · 2023Article
Corrections and comments
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Authors and funding
22 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Poly ADP-ribose polymerase inhibitors (PARPi) have transformed ovarian cancer (OC) treatment, primarily for tumours deficient in homologous recombination repair. Combining VEGF-signalling inhibitors with PARPi has enhanced clinical benefit in OC. To study drivers of efficacy when combining PARP inhibition and VEGF-signalling, a cohort of patient-derived ovarian cancer xenografts (OC-PDXs), representative of the molecular characteristics and drug sensitivity of patient tumours, were treated with the PARPi olaparib and the VEGFR inhibitor cediranib at clinically relevant doses. The combination showed broad anti-tumour activity, reducing growth of all OC-PDXs, regardless of the homologous recombination repair (HRR) mutational status, with greater additive combination benefit in tumours poorly sensitive to platinum and olaparib. In orthotopic models, the combined treatment reduced tumour dissemination in the peritoneal cavity and prolonged survival. Enhanced combination benefit was independent of tumour cell expression of receptor tyrosine kinases targeted by cediranib, and not associated with change in expression of genes associated with DNA repair machinery. However, the combination of cediranib with olaparib was effective in reducing tumour vasculature in all the OC-PDXs. Collectively our data suggest that olaparib and cediranib act through complementary mechanisms affecting tumour cells and tumour microenvironment, respectively. This detailed analysis of the combined effect of VEGF-signalling and PARP inhibitors in OC-PDXs suggest that despite broad activity, there is no dominant common mechanistic inter-dependency driving therapeutic benefit.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.