ArticleProceedings of the National Academy of Sciences of the United States of America2014
Hypoxia-inducible factors are required for chemotherapy resistance of breast cancer stem cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 280 papers.
What it found
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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
280 citing papers in PubMed, 461 citations in OpenAlex.
- A randomized, placebo-controlled phase 2 study of paclitaxel in combination with reparixin compared to paclitaxel alone as front-line therapy for metastatic triple-negative breast cancer (fRida).Breast cancer research and treatment · 2021Trial
- A window-of-opportunity trial of the CXCR1/2 inhibitor reparixin in operable HER-2-negative breast cancer.Breast cancer research : BCR · 2020Trial
- Influence of RNA Modifications on Cancer Metabolism: Interplay with Hypoxia and Therapeutic Implications.Advances in experimental medicine and biology · 2026Review
- Organic Sonosensitizers-based SDT with enhanced ROS generation.Ultrasonics sonochemistry · 2025Review
- Rotenoids from the Roots of Vicia faba L. (Fabaceae): Structural Characterization, Cytotoxic Effects, and Molecular Docking.Chemistry & biodiversity · 2025Article
- Hypoxia-inducible factors in breast cancer: prognostic indicators and emerging biomarkers: narrative review.Annals of medicine and surgery (2012) · 2025Review
- Oxygen gradients in tumor tissues implications for breast cancer metastasis - a narrative review.Annals of medicine and surgery (2012) · 2025Review
- Targeting Triple-Negative Breast Cancer: Resistance Mechanisms and Therapeutic Advancements.Cancer medicine · 2025Review
- A Novel 3D High-Throughput Phenotypic Drug Screening Pipeline to Identify Drugs with Repurposing Potential for the Treatment of Ovarian Cancer.Advanced healthcare materials · 2025Article
- Direct inhibition of tumor hypoxia response with synthetic transcriptional repressors.Nature chemical biology · 2025Article
- Identification of robust RT-qPCR reference genes for studying changes in gene expression in response to hypoxia in breast cancer cell lines.BMC genomics · 2025Article
- Toll-Like receptor 3-mediated interferon-β production is suppressed by oncostatin m and a broader epithelial-mesenchymal transition program.Breast cancer research : BCR · 2024Article
- The p-MYH9/USP22/HIF-1α axis promotes lenvatinib resistance and cancer stemness in hepatocellular carcinoma.Signal transduction and targeted therapy · 2024Article
- Genetically engineered nanomodulators elicit potent immunity against cancer stem cells by checkpoint blockade and hypoxia relief.Bioactive materials · 2024Article
- Nanomaterial-related hemoglobin-based oxygen carriers, with emphasis on liposome and nano-capsules, for biomedical applications: current status and future perspectives.Journal of nanobiotechnology · 2024Review
- Tumor microenvironment of cancer stem cells: Perspectives on cancer stem cell targeting.Genes & diseases · 2024Review
- Hypomethylation of ATP1A1 Is Associated with Poor Prognosis and Cancer Progression in Triple-Negative Breast Cancer.Cancers · 2024Article
- Transcriptional elongation control of hypoxic response.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Hypoxia, oxidative stress, and the interplay of HIFs and NRF2 signaling in cancer.Experimental & molecular medicine · 2024Review
- Review
220 more citing papers are in PubMed but not listed here.
Corrections and comments
- Retraction · 2022-09-02Concerns/Issues about Data · Concerns/Issues about Image · Duplication of Data ·
- Retracted
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Triple negative breast cancers (TNBCs) are defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 expression, and are treated with cytotoxic chemotherapy such as paclitaxel or gemcitabine, with a durable response rate of less than 20%. TNBCs are enriched for the basal subtype gene expression profile and the presence of breast cancer stem cells, which are endowed with self-renewing and tumor-initiating properties and resistance to chemotherapy. Hypoxia-inducible factors (HIFs) and their target gene products are highly active in TNBCs. Here, we demonstrate that HIF expression and transcriptional activity are induced by treatment of MDA-MB-231, SUM-149, and SUM-159, which are human TNBC cell lines, as well as MCF-7, which is an ER(+)/PR(+) breast cancer line, with paclitaxel or gemcitabine. Chemotherapy-induced HIF activity enriched the breast cancer stem cell population through interleukin-6 and interleukin-8 signaling and increased expression of multidrug resistance 1. Coadministration of HIF inhibitors overcame the resistance of breast cancer stem cells to paclitaxel or gemcitabine, both in vitro and in vivo, leading to tumor eradication. Increased expression of HIF-1α or HIF target genes in breast cancer biopsies was associated with decreased overall survival, particularly in patients with basal subtype tumors and those treated with chemotherapy alone. Based on these results, clinical trials are warranted to test whether treatment of patients with TNBC with a combination of cytotoxic chemotherapy and HIF inhibitors will improve patient survival.
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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.