ArticleBMC cancer2014
Chk1 inhibition as a novel therapeutic strategy for treating triple-negative breast and ovarian cancers.
Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 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
70 citing papers in PubMed, 110 citations in OpenAlex.
- Integrated network pharmacology reveal new key curcumin-binding targets in triple-negative breast cancer.Discover oncology · 2026Article
- Immune cell-related gene signatures for diagnostic and prognostic stratification in thyroid cancer using machine learning analysis.Discover oncology · 2026Article
- CHEK1 Expression Correlates with Tumor Progression in Lung Adenocarcinoma but Not in Squamous Cell Carcinoma.Medicina (Kaunas, Lithuania) · 2026Article
- Biomarkers and potential function analysis of triple-negative breast cancer screening based on bioinformatics.Cancer biomarkers : section A of Disease markers · 2025Article
- Insights into the Emerging Therapeutic Targets of Triple-negative Breast Cancer.Current cancer drug targets · 2025Review
- Article
- Single-cell transcriptional atlas of human breast cancers and model systems.Clinical and translational medicine · 2024Article
- DNA damage response in breast cancer and its significant role in guiding novel precise therapies.Biomarker research · 2024Review
- CHK1 inhibitor induced PARylation by targeting PARG causes excessive replication and metabolic stress and overcomes chemoresistance in ovarian cancer.Cell death discovery · 2024Article
- Triple-Negative Breast Cancer and Emerging Therapeutic Strategies: ATR and CHK1/2 as Promising Targets.Cancers · 2024Review
- CHEK2 signaling is the key regulator of oocyte survival after chemotherapy.Science advances · 2023Article
- CRISPR/Cas9 mediated knocking out of OPN gene enhances radiosensitivity in MDA-MB-231 breast cancer cell line.Journal of cancer research and clinical oncology · 2023Article
- DNA Damage Response Alterations in Ovarian Cancer: From Molecular Mechanisms to Therapeutic Opportunities.Cancers · 2023Review
- Checkpoint Kinase 1 (CHK1) Functions as Both a Diagnostic Marker and a Regulator of Epithelial-to-Mesenchymal Transition (EMT) in Triple-Negative Breast Cancer.Current issues in molecular biology · 2022Article
- DNA damage response revisited: the p53 family and its regulators provide endless cancer therapy opportunities.Experimental & molecular medicine · 2022Review
- Chk1 inhibitor-induced DNA damage increases BFL1 and decreases BIM but does not protect human cancer cell lines from Chk1 inhibitor-induced apoptosis.American journal of cancer research · 2022Article
- The developing landscape of combinatorial therapies of immune checkpoint blockade with DNA damage repair inhibitors for the treatment of breast and ovarian cancers.Journal of hematology & oncology · 2021Review
- The cytosolic iron-sulfur cluster assembly (CIA) pathway is required for replication stress tolerance of cancer cells to Chk1 and ATR inhibitors.NPJ breast cancer · 2021Article
- A phase 1 study of prexasertib (LY2606368), a CHK1/2 inhibitor, in pediatric patients with recurrent or refractory solid tumors, including CNS tumors: A report from the Children's Oncology Group Pediatric Early Phase Clinical Trials Network (ADVL1515).Pediatric blood & cancer · 2021Article
- Review
10 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
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChk1 inhibitors are currently in clinical trials as putative potentiators of cytotoxic chemotherapy drugs. Chk1 inhibitors may exhibit single agent anti-tumor activity in cancers with underlying DNA repair, DNA damage response or DNA replication defects.
methodsHere we describe the cellular effects of the pharmacological inhibition of the checkpoint kinase Chk1 by the novel inhibitor V158411 in triple-negative breast cancer and ovarian cancer. Cytotoxicity, the effect on DNA damage response and cell cycle along with the ability to potentiate gemcitabine and cisplatin cytotoxicity in cultured cells was investigated. Western blotting of proteins involved in DNA repair, checkpoint activation, cell cycle and apoptosis was used to identify potential predictive biomarkers of Chk1 inhibitor sensitivity.
resultsThe Chk1 inhibitors V158411, PF-477736 and AZD7762 potently inhibited the proliferation of triple-negative breast cancer cells as well as ovarian cancer cells, and these cell lines were sensitive compared to ER positive breast and other solid cancer cells lines. Inhibition of Chk1 in these sensitive cell lines induced DNA damage and caspase-3/7 dependent apoptosis. Western blot profiling identified pChk1 (S296) as a predictive biomarker of Chk1 inhibitor sensitivity in ovarian and triple-negative breast cancer and pH2AX (S139) in luminal breast cancer.
conclusionsThis finding suggests that Chk1 inhibitors either as single agents or in combination chemotherapy represents a viable therapeutic option for the treatment of triple-negative breast cancer. pChk1 (S296) tumor expression levels could serve as a useful biomarker to stratify patients who might benefit from Chk1 inhibitor therapy.
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.