ArticleOncogene2020
Resistance to the CHK1 inhibitor prexasertib involves functionally distinct CHK1 activities in BRCA wild-type ovarian cancer.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 56 citations in OpenAlex.
- The CHK1 inhibitor prexasertib in BRCA wild-type platinum-resistant recurrent high-grade serous ovarian carcinoma: a phase 2 trial.Nature communications · 2024Trial
- Trial
- A Phase 2 study of prexasertib (LY2606368) in platinum resistant or refractory recurrent ovarian cancer.Gynecologic oncology · 2022Trial
- Aberrant expression of GBP5 in tumor-infiltrating immune cells as an onco-immunological biomarker in pan-cancer.Discover oncology · 2026Article
- Nuclear factor IX promotes endometriosis progression through transcriptional activation of tetraspanin-2.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Longitudinal prediction of drug response in high-grade serous ovarian cancer organoid cultures aligning with clinical responses.Journal of advanced research · 2026Article
- Transcriptional Profiling Reveals Lineage-Specific Characteristics in ATR/CHK1 Inhibitor-Resistant Endometrial Cancer.Biomolecules · 2026Article
- The CHK1 inhibitor Prexasertib is effective againstFrontiers in endocrinology · 2026Article
- Targeting DNA repair mechanisms in cancer therapy: the role of small molecule DNA repair inhibitors.NAR cancer · 2025Review
- Article
- Antitumor Activity of Radiation Therapy Combined with Checkpoint Kinase Inhibition in SHH/International journal of molecular sciences · 2025Article
- Targeting ANXA4 to Overcome Cisplatin Resistance in Ovarian Cancer: A Bioinformatics and in Vitro Study.OncoTargets and therapy · 2025Article
- Distinct effects of sacituzumab govitecan and berzosertib on DNA damage response in ovarian cancer.iScience · 2024Article
- Review
- AKT1 interacts with DHX9 to Mitigate R Loop-Induced Replication Stress in Ovarian Cancer.Cancer research · 2024Article
- Key Proteins of Replication Stress Response and Cell Cycle Control as Cancer Therapy Targets.International journal of molecular sciences · 2024Review
- Olaparib-ResistantCells · 2023Article
- DNA Damage Response Alterations in Ovarian Cancer: From Molecular Mechanisms to Therapeutic Opportunities.Cancers · 2023Review
- StabJGL: a stability approach to sparsity and similarity selection in multiple-network reconstruction.Bioinformatics advances · 2023Article
- Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
High grade serous ovarian cancer (HGSOC) is a fatal gynecologic malignancy in the U.S. with limited treatment options. New therapeutic strategies include targeting of the cell cycle checkpoints, e.g., ATR and CHK1. We recently reported a promising clinical activity of the CHK1 inhibitor (CHK1i) prexasertib monotherapy in BRCA wild-type (BRCAwt) HGSOC patients. In this study, biopsies of treated patients and cell line models were used to investigate possible mechanisms of resistance to CHK1i. We report that BRCAwt HGSOC develops resistance to prexasertib monotherapy via a prolonged G2 delay induced by lower CDK1/CyclinB1 activity, thus preventing cells from mitotic catastrophe and cell death. On the other hand, we noted CHK1's regulation on RAD51-mediated homologous recombination (HR) repair was not altered in CHK1i-resistant cells. Therefore, CHK1i sensitizes CHK1i-resistant cells to DNA damaging agents such as gemcitabine or hydroxyurea by inhibition of HR. In summary, our results demonstrate new mechanistic insights of functionally distinct CHK1 activities and highlight a potential combination treatment approach to overcome CHK1i resistance in BRCAwt HGSOC.
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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.