ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
The CHK1 Inhibitor Prexasertib Exhibits Monotherapy Activity in High-Grade Serous Ovarian Cancer Models and Sensitizes to PARP Inhibition.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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The trial behind it
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Who cites it
99 citing papers in PubMed, 143 citations in OpenAlex.
- Trial
- A Phase 2 study of prexasertib (LY2606368) in platinum resistant or refractory recurrent ovarian cancer.Gynecologic oncology · 2022Trial
- Dual targeting of the DNA damage response pathway and BCL-2 in diffuse large B-cell lymphoma.Leukemia · 2022Trial
- Chromosomal instability in cancer: sources, consequences and new therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- Review
- BAYESIAN EMPIRICAL LIKELIHOOD FOR ULTRA-HIGH DIMENSIONAL VARIABLE SELECTION WITH APPLICATION TO DRUG SENSITIVITY.The annals of applied statistics · 2026Article
- PTEN deficiency confers sensitivity to ATR inhibitor-based treatment in high-grade serous ovarian cancer.The Journal of clinical investigation · 2026Article
- Using targeted therapy to promote a pro-inflammatory tumour microenvironment and anti-tumour immune response in high grade serous ovarian cancer.British journal of cancer · 2026Article
- Increased vulnerability of colorectal cancer models with high alkylation damage to NTHL1 inactivation.Scientific reports · 2026Article
- Clinical application of PARP inhibitors and emerging strategies to overcome resistance: a pan-cancer perspective.Biomarker research · 2026Review
- Targeting de novo pyrimidine synthesis confers vulnerability to copper-mediated ATR inactivation in PARP inhibitor-resistant ovarian cancer.Nature communications · 2026Article
- NSMF modulates replication stress to facilitate colorectal cancer progression.Nucleic acids research · 2026Article
- CHK1 as a Metabolic and Immunological Regulator: Implications for Cancer Therapy.Oncology research · 2026Review
- Uncovering ShuangZi Powder's Anti-Ovarian Cancer Mechanism: A Systems Biology and Experimental Approach.Combinatorial chemistry & high throughput screening · 2026Article
- Unraveling the Resistance: Challenges and Advances in PARP Inhibitor Therapy for BRCA1/2 Breast Cancer.Anti-cancer agents in medicinal chemistry · 2026Review
- Targeting DNA repair mechanisms in cancer therapy: the role of small molecule DNA repair inhibitors.NAR cancer · 2025Review
- Distinct Chemical Cues Reprogram Cellular and Multicellular Phenotypes in Ovarian Cancer Spheroids.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Targeting DNA Damage Repair Pathways Beyond PARP Inhibition.Targeted oncology · 2025Review
- Targeting Replication Fork Processing Synergizes with PARP Inhibition to Potentiate Lethality in Homologous Recombination Proficient Ovarian Cancers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- TAOK1 promotes filament formation in HR repair through phosphorylating USP7.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
39 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 1 country.
Funding
Abstract
purposePARP inhibitors are approved for the treatment of high-grade serous ovarian cancers (HGSOC). Therapeutic resistance, resulting from restoration of homologous recombination (HR) repair or replication fork stabilization, is a pressing clinical problem. We assessed the activity of prexasertib, a checkpoint kinase 1 (CHK1) inhibitor known to cause replication catastrophe, as monotherapy and in combination with the PARP inhibitor olaparib in preclinical models of HGSOC, including those with acquired PARP inhibitor resistance. EXPERIMENTAL
designPrexasertib was tested as a single agent or in combination with olaparib in 14 clinically annotated and molecularly characterized luciferized HGSOC patient-derived xenograft (PDX) models and in a panel of ovarian cancer cell lines. The ability of prexasertib to impair HR repair and replication fork stability was also assessed.
resultsPrexasertib monotherapy demonstrated antitumor activity across the 14 PDX models. Thirteen models were resistant to olaparib monotherapy, including 4 carrying
conclusionsPrexasertib exhibits monotherapy activity in PARP inhibitor-resistant HGSOC PDX and cell line models, reverses restored HR and replication fork stability, and synergizes with PARP inhibition.
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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.