Trial reportNature communications2021
A Replication stress biomarker is associated with response to gemcitabine versus combined gemcitabine and ATR inhibitor therapy in ovarian cancer.
Trial report in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
46 citing papers in PubMed, 67 citations in OpenAlex.
- A Phase II Study of Berzosertib in Combination with Carboplatin Compared with Docetaxel with Carboplatin in Metastatic Castration-Resistant Prostate Cancer.Cancer research communications · 2026Trial
- Randomized Phase II Study of Gemcitabine With or Without ATR Inhibitor Berzosertib in Platinum-Resistant Ovarian Cancer: Final Overall Survival and Biomarker Analyses.JCO precision oncology · 2024Trial
- The CHK1 inhibitor prexasertib in BRCA wild-type platinum-resistant recurrent high-grade serous ovarian carcinoma: a phase 2 trial.Nature communications · 2024Trial
- Trial
- PTEN deficiency confers sensitivity to ATR inhibitor-based treatment in high-grade serous ovarian cancer.The Journal of clinical investigation · 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
- APOBEC3C coordinates DDX5 in R-loop resolution and dynamic control of Chk1-mediated stress-responsive circuitry as a prerequisite for gemcitabine resistance in p53-deficient cells.Cell death & disease · 2026Article
- ZMYM3 S464: a potential phospho-regulatory hub in epigenetic remodeling and oncogenesis.Molecular genetics and genomics : MGG · 2026Article
- Fadraciclib, a CDK2/CDK9 inhibitor, shows efficacy in biliary tract cancer and synergistic potential with olaparib and JQ1 based on MCL1 expression.Cell communication and signaling : CCS · 2025Article
- Targeting E2F8 sensitizes gemcitabine-resistant gallbladder cancer to PARP inhibitors by disrupting RRM2-driven DNA repair.Journal of experimental & clinical cancer research : CR · 2025Article
- FSTL3 is a biomarker of poor prognosis and associated with immunotherapy resistance in ovarian cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Navigating PARP Inhibitor Resistance in Ovarian Cancer: Bridging Mechanistic Insights To Clinical Translation.Current treatment options in oncology · 2025Review
- The RING finger E3 ligase RNF25 protects DNA replication forks independently of its canonical roles in ubiquitin signaling.Nature communications · 2025Article
- Phospho-RPA2 predicts response to platinum and PARP inhibitors in homologous recombination-proficient ovarian cancer.The Journal of clinical investigation · 2025Article
- Article
- Precision Medicine in High-Grade Serous Ovarian Cancer: Targeted Therapies and the Challenge of Chemoresistance.International journal of molecular sciences · 2025Review
- The RING Finger E3 Ligase RNF25 Protects DNA Replication Forks Independently of its Canonical Roles in Ubiquitin Signaling.bioRxiv : the preprint server for biology · 2025Article
- DNA damage response inhibitors in cancer therapy: lessons from the past, current status and future implications.Nature reviews. Drug discovery · 2025Review
- Targeting synthetic lethality: an effective therapeutic approach in ovarian and endometrial cancers.Therapeutic advances in medical oncology · 2025Review
- Targeting the DNA damage response in cancer.MedComm · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 7 institutions in 3 countries.
Funding
Abstract
In a trial of patients with high grade serous ovarian cancer (HGSOC), addition of the ATR inhibitor berzosertib to gemcitabine improved progression free survival (PFS) compared to gemcitabine alone but biomarkers predictive of treatment are lacking. Here we report a candidate biomarker of response to gemcitabine versus combined gemcitabine and ATR inhibitor therapy in HGSOC ovarian cancer. Patients with replication stress (RS)-high tumors (n = 27), defined as harboring at least one genomic RS alteration related to loss of RB pathway regulation and/or oncogene-induced replication stress achieve significantly prolonged PFS (HR = 0.38, 90% CI, 0.17-0.86) on gemcitabine monotherapy compared to those with tumors without such alterations (defined as RS-low, n = 30). However, addition of berzosertib to gemcitabine benefits only patients with RS-low tumors (gemcitabine/berzosertib HR 0.34, 90% CI, 0.13-0.86) and not patients with RS-high tumors (HR 1.11, 90% CI, 0.47-2.62). Our findings support the notion that the exacerbation of RS by gemcitabine monotherapy is adequate for lethality in RS-high tumors. Conversely, for RS-low tumors addition of berzosertib-mediated ATR inhibition to gemcitabine is necessary for lethality to occur. Independent prospective validation of this biomarker is required.
Indexed as
Identifiers
What OpenQuestion holds
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.