ArticleThe Journal of clinical investigation2012
Targeting Chk1 in p53-deficient triple-negative breast cancer is therapeutically beneficial in human-in-mouse tumor models.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 136 papers, 1 of them a synthesis that pooled it.
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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
136 citing papers in PubMed, 1 synthesis or guideline pooled it, 222 citations in OpenAlex.
- Advances in the Prevention and Treatment of Obesity-Driven Effects in Breast Cancers.Frontiers in oncology · 2022Pooled it
- An Annotated Biobank of Triple-Negative Breast Cancer Patient-Derived Xenografts Features Treatment-Naïve and Longitudinal Samples during Neoadjuvant Chemotherapy.Cancer research · 2025Trial
- A Phase II Single Arm Pilot Study of the CHK1 Inhibitor Prexasertib (LY2606368) in BRCA Wild-Type, Advanced Triple-Negative Breast Cancer.The oncologist · 2020Trial
- A Phase II Trial of Neoadjuvant MK-2206, an AKT Inhibitor, with Anastrozole in Clinical Stage II or IIIClinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- Targeting an IKBKE cytokine network impairs triple-negative breast cancer growth.The Journal of clinical investigation · 2014Trial
- A phase II study of UCN-01 in combination with irinotecan in patients with metastatic triple negative breast cancer.Breast cancer research and treatment · 2013Trial
- Aging and cancer: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- Integrated network pharmacology reveal new key curcumin-binding targets in triple-negative breast cancer.Discover oncology · 2026Article
- Inhibition of GPX4 induces the death of p53-mutant triple-negative breast cancer cells.Breast cancer research and treatment · 2026Article
- Article
- Review
- The leading role of MYC in DNA damage response: exploring opportunities for therapeutic inhibition.Frontiers in cell and developmental biology · 2025Review
- Role of artificial intelligence in cancer detection using protein p53: A Review.Molecular biology reports · 2024Review
- Polθ: emerging synthetic lethal partner in homologous recombination-deficient tumors.Cancer gene therapy · 2024Review
- Single-cell transcriptional atlas of human breast cancers and model systems.Clinical and translational medicine · 2024Article
- The treatment landscape of triple-negative breast cancer.Medical oncology (Northwood, London, England) · 2024Review
- Article
- Distinct Regulation of ASCL1 by the Cell Cycle and Chemotherapy in Small Cell Lung Cancer.Molecular cancer research : MCR · 2024Article
- The thioredoxin system determines CHK1 inhibitor sensitivity via redox-mediated regulation of ribonucleotide reductase activity.Nature communications · 2024Article
- Novel Amidine Derivative K1586 Sensitizes Colorectal Cancer Cells to Ionizing Radiation by Inducing Chk1 Instability.International journal of molecular sciences · 2024Article
76 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Patients with triple-negative breast cancer (TNBC) - defined by lack of estrogen receptor and progesterone receptor expression as well as lack of human epidermal growth factor receptor 2 (HER2) amplification - have a poor prognosis. There is a need for targeted therapies to treat this condition. TNBCs frequently harbor mutations in TP53, resulting in loss of the G1 checkpoint and reliance on checkpoint kinase 1 (Chk1) to arrest cells in response to DNA damage. Previous studies have shown that inhibition of Chk1 in a p53-deficient background results in apoptosis [corrected] in response to DNA damage. We therefore tested whether inhibition of Chk1 could potentiate the cytotoxicity of the DNA damaging agent irinotecan in TNBC using xenotransplant tumor models. Tumor specimens from patients with TNBC were engrafted into humanized mammary fat pads of immunodeficient mice to create 3 independent human-in-mouse TNBC lines: 1 WT (WU-BC3) and 2 mutant for TP53 (WU-BC4 and WU-BC5). These lines were tested for their response to irinotecan and a Chk1 inhibitor (either UCN-01 or AZD7762), either as single agents or in combination. The combination therapy induced checkpoint bypass and apoptosis in WU-BC4 and WU-BC5, but not WU-BC3, tumors. Moreover, combination therapy inhibited tumor growth and prolonged survival of mice bearing the WU-BC4 line, but not the WU-BC3 line. In addition, knockdown of p53 sensitized WU-BC3 tumors to the combination therapy. These results demonstrate that p53 is a major determinant of how TNBCs respond to therapies that combine DNA damage with Chk1 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.