ArticleCancer research2013
ATR inhibition broadly sensitizes ovarian cancer cells to chemotherapy independent of BRCA status.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02723864 (Phase I Study of Veliparib), which is not on this map. Cited by 127 papers, 1 of them a synthesis that pooled it.
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.
Phase I Study of Veliparib (ABT-888), an Oral PARP Inhibitor, and VX-970, an ATR Inhibitor in Combination With Cisplatin in Patients With Refractory Solid Tumors
Who cites it
127 citing papers in PubMed, 1 synthesis or guideline pooled it, 208 citations in OpenAlex.
- Analysis from the perspective of cilia: the protective effect of PARP inhibitors on visual function during light-induced damage.International ophthalmology · 2020Pooled it
- Combination ATR and PARP Inhibitor (CAPRI): A phase 2 study of ceralasertib plus olaparib in patients with recurrent, platinum-resistant epithelial ovarian cancer.Gynecologic oncology · 2021Trial
- A Replication stress biomarker is associated with response to gemcitabine versus combined gemcitabine and ATR inhibitor therapy in ovarian cancer.Nature communications · 2021Trial
- Berzosertib plus gemcitabine versus gemcitabine alone in platinum-resistant high-grade serous ovarian cancer: a multicentre, open-label, randomised, phase 2 trial.The Lancet. Oncology · 2020Trial
- Sensitizing Colorectal Cancer to PARP Inhibitors: Biomarkers, Mechanisms, and Combination Strategies.International journal of molecular sciences · 2026Review
- Plasticity of Non-Apoptotic Residual Tumor Cells After Neoadjuvant Immunochemotherapy: Epigenetic and Microenvironmental Determinants.Biomolecules · 2026Review
- Common DNA Damage Response Factors Required for Cellular Resistance to Inhibitors for the Ataxia Telangiectasia and Rad3-Related Checkpoint Kinase in Hematopoietic Cells.Biomolecules · 2026Article
- AZD6738 overcomes acquired olaparib resistance in BRCA1 mutation triple-negative breast cancer through down-regulation of BRCA2 and RAD51.Scientific reports · 2026Article
- Camonsertib, an ATRi, in Combination with Low-Dose Gemcitabine in Solid Tumors with DNA Damage Response Aberrations: Preclinical and Phase Ib Results.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Targeting DNA Topoisomerase I for the Treatment of Cancer: Past, Present and Future.Journal of molecular biology · 2026Review
- Dual FAK and EPHA2 targeting by brigatinib tackles PARP inhibitor adaptive survival response in high-grade serous ovarian cancer.Science translational medicine · 2026Article
- Auranofin attenuates TOPBP1-mediated ATR replication stress response and improves chemotherapeutic response in breast tumor models.The Journal of clinical investigation · 2025Article
- Translational Aspects of DNA Damage Repair in Optimizing Cancer Chemotherapy.Advanced genetics (Hoboken, N.J.) · 2025Review
- Medicinal chemistry breakthroughs on ATM, ATR, and DNA-PK inhibitors as prospective cancer therapeutics.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Review
- Novel ATR/PARP1 Dual Inhibitors Demonstrate Synergistic Antitumor Efficacy in Triple-Negative Breast Cancer Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Emerging roles of the cancerous inhibitor of protein phosphatase 2A (CIP2A) in ovarian cancer.Scientific reports · 2025Article
- Safety and Tolerability of Berzosertib, an Ataxia-Telangiectasia-Related Inhibitor, and Veliparib, an Oral Poly (ADP-ribose) Polymerase Inhibitor, in Combination With Cisplatin in Patients With Refractory Solid Tumors.JCO precision oncology · 2025Article
- Olaparib Combined with DDR Inhibitors Effectively Prevents EMT and Affects miRNA Regulation inInternational journal of molecular sciences · 2025Article
- Distinct effects of sacituzumab govitecan and berzosertib on DNA damage response in ovarian cancer.iScience · 2024Article
67 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Replication stress and DNA damage activate the ATR-Chk1 checkpoint signaling pathway that licenses repair and cell survival processes. In this study, we examined the respective roles of the ATR and Chk1 kinases in ovarian cancer cells using genetic and pharmacologic inhibitors in combination with cisplatin, topotecan, gemcitabine, and the PARP inhibitor veliparib (ABT-888), four agents with clinical activity in ovarian cancer. RNA interference (RNAi)-mediated depletion or inhibition of ATR sensitized ovarian cancer cells to all four agents. In contrast, while cisplatin, topotecan, and gemcitabine each activated Chk1, RNAi-mediated depletion or inhibition of this kinase in cells sensitized them only to gemcitabine. Unexpectedly, we found that neither the ATR kinase inhibitor VE-821 nor the Chk1 inhibitor MK-8776 blocked ATR-mediated Chk1 phosphorylation or autophosphorylation, two commonly used readouts for inhibition of the ATR-Chk1 pathway. Instead, their ability to sensitize cells correlated with enhanced CDC25A levels. In addition, we also found that VE-821 could further sensitize BRCA1-depleted cells to cisplatin, topotecan, and veliparib beyond the potent sensitization already caused by their deficiency in homologous recombination. Taken together, our results established that ATR and Chk1 inhibitors differentially sensitize ovarian cancer cells to commonly used chemotherapy agents and that Chk1 phosphorylation status may not offer a reliable marker for inhibition of the ATR-Chk1 pathway. A key implication of our work is the clinical rationale it provides to evaluate ATR inhibitors in combination with PARP inhibitors in BRCA1/2-deficient cells.
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.