ArticleInternational journal of molecular sciences2020
Targeting Hypoxia Sensitizes TNBC to Cisplatin and Promotes Inhibition of Both Bulk and Cancer Stem Cells.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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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.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Bioactive Natural Compounds in Triple-Negative Breast Cancer: Molecular Targets and Therapeutic Perspectives.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Breast Cancer: Challenges in the Treatment and Prodrug Strategies.Mini reviews in medicinal chemistry · 2026Review
- Metformin-Based Combination Approaches for Triple-Negative Breast Cancer.Pharmaceutics · 2025Review
- Targeting Tumor Hypoxia with Nanoparticle-Based Therapies: Challenges, Opportunities, and Clinical Implications.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Harnessing adrenergic blockade in stress-promoted TNBCFrontiers in pharmacology · 2024Article
- Anti-ENO1 antibody combined with metformin against tumor resistance: a novel antibody-based platform.PeerJ · 2024Article
- Overexpression of cannabinoid receptor 2 is associated with human breast cancer proliferation, apoptosis, chemosensitivity and prognosis via the PI3K/Akt/mTOR signaling pathway.Cancer medicine · 2023Article
- Dynamic tumor microenvironment, molecular heterogeneity, and distinct immunologic portrait of triple-negative breast cancer: an impact on classification and treatment approaches.Breast cancer (Tokyo, Japan) · 2023Review
- Adaptation to Hypoxia May Promote Therapeutic Resistance to Androgen Receptor Inhibition in Triple-Negative Breast Cancer.International journal of molecular sciences · 2022Review
- Metformin Can Enhance the Inhibitory Effect of Olaparib in Bladder Cancer Cells.Disease markers · 2022Article
- Clinically Translatable Approaches of Inhibiting TGF-β to Target Cancer Stem Cells in TNBC.Biomedicines · 2021Review
- Advances in Liver Cancer Stem Cell Isolation and their Characterization.Stem cell reviews and reports · 2021Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Development of targeted therapies for triple-negative breast cancer (TNBC) is an unmet medical need. Cisplatin has demonstrated its promising potential for the treatment of TNBC in clinical trials; however, cisplatin treatment is associated with hypoxia that, in turn, promotes cancer stem cell (CSC) enrichment and drug resistance. Therapeutic approaches to attenuate this may lead to increased cisplatin efficacy in the clinic for the treatment of TNBC. In this report we analyzed clinical datasets of TNBC and found that TNBC patients possessed higher levels of EGFR and hypoxia gene expression. A similar expression pattern was also observed in cisplatin-resistant ovarian cancer cells. We, thus, developed a new therapeutic approach to inhibit EGFR and hypoxia by combination treatment with metformin and gefitinib that sensitized TNBC cells to cisplatin and led to the inhibition of both CD44+/CD24- and ALDH+ CSCs. We demonstrated a similar inhibition efficacy on organotypic cultures of TNBC patient samples ex vivo. Since these drugs have already been used frequently in the clinic; this study illustrates a novel, clinically translatable therapeutic approach to treat patients with TNBC.
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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.