ArticleThe AAPS journal2020
In Vitro and In Vivo Efficacy of AZD3965 and Alpha-Cyano-4-Hydroxycinnamic Acid in the Murine 4T1 Breast Tumor Model.
Article in The AAPS journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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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
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Prognostic Value of Monocarboxylate Transporter 1 Overexpression in Cancer: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Methylglyoxal AttenuatesInternational journal of molecular sciences · 2026Article
- Lactylation in cancer: molecular mechanisms and advances in clinical study.Molecular cancer · 2026Review
- The lactate-lactylation axis in tumor radioresistance: metabolic, epigenetic, and immune mechanisms with emerging links to RNA regulation.Frontiers in immunology · 2026Review
- Glycolysis and glycolytic enzymes in acute myeloid leukemia: Warburg and beyond.Frontiers in pharmacology · 2026Review
- Aerobic glycolysis-driven lactate accumulation and acidic tumor microenvironment in hepatocellular carcinoma: a vicious cycle promoting tumor progression.Frontiers in pharmacology · 2026Review
- Itaconate transport across the plasma membrane and Salmonella-containing vacuole via MCT1/4 modulates macrophage antibacterial activity.Nature communications · 2025Article
- Lactate at the crossroads of tumor metabolism and immune escape: a new frontier in cancer therapy.Journal of translational medicine · 2025Review
- Myeloid metabolism and its role in immunotherapy of cancer.Journal for immunotherapy of cancer · 2025Review
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- Glyco Ionic Liquids as Novel Nanoparticle Coatings to Enhance Triple-Negative Breast Cancer Drug Delivery.Advanced healthcare materials · 2025Article
- Nonhistone lactylation: A hub for tumour metabolic reprogramming and epigenetic regulation.Journal of translational medicine · 2025Review
- Lactate-Mediated Crosstalk Between Tumor Cells and Cancer-Associated Fibroblasts: Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- Lactate and lactylation in cancer.Signal transduction and targeted therapy · 2025Review
- MCT4 inhibition attenuates inflammatory response toFrontiers in immunology · 2025Article
- Insights into recent findings and therapeutic potential of nonhistone lactylation in cancer.Frontiers in molecular biosciences · 2025Review
- The role of lactylation in breast cancer development: mechanisms, clinical translation and new strategies for treatment.Frontiers in oncology · 2025Review
- The interplay between the tumor microenvironment and tumor-derived small extracellular vesicles in cancer development and therapeutic response.Cancer biology & therapy · 2024Review
- In Vitro and In Vivo Antitumor Activities of Isothiourea and Cinnamic Acid Derivative with NOS/MCT Inhibitory Effect.Bulletin of experimental biology and medicine · 2024Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Monocarboxylate transporter 1 (MCT1) represents a potential therapeutic target in cancer. The objective of this study was to determine the efficacy of AZD3965 (a specific inhibitor of MCT1) and α-cyano-4-hydroxycinnamic acid (CHC, a nonspecific inhibitor of MCTs) in the murine 4T1 tumor model of triple-negative breast cancer (TNBC). Expression of MCT1 and MCT4 in 4T1 and mouse mammary epithelial cells were determined by Western blot. Inhibition of MCT1-mediated L-lactate uptake and cellular proliferation by AZD3965 and CHC was determined. Mice bearing 4T1 breast tumors were treated with AZD3965 100 mg/kg i.p. twice-daily or CHC 200 mg/kg i.p. once-daily. Tumor growth, metastasis, intra-tumor lactate concentration, immune function, tumor MCT expression, and concentration-effect relationships were determined. AZD3965 and CHC inhibited cell growth and L-lactate uptake in 4T1 cells. AZD3965 treatment resulted in trough plasma and tumor concentrations of 29.1 ± 13.9 and 1670 ± 946 nM, respectively. AZD3965 decreased the tumor proliferation biomarker Ki67 expression, increased intra-tumor lactate concentration, and decreased tumor volume, although tumor weight was not different from untreated controls. CHC had no effect on tumor volume and weight, or intra-tumor lactate concentration. AZD3965 treatment reduced the blood leukocyte count and spleen weight and increased lung metastasis, while CHC did not. These findings indicate AZD3965 is a potent MCT1 inhibitor that accumulates to high concentrations in 4T1 xenograft tumors, where it increases tumor lactate concentrations and produces beneficial effects on markers of TNBC; however, overall effects on tumor growth were minimal and lung metastases increased.
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