ArticleCancers2021
In Vitro and In Vivo Characterization of MCT1 Inhibitor AZD3965 Confirms Preclinical Safety Compatible with Breast Cancer Treatment.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- The mechanism of breast cancer stem cells and tumor microenvironment promoting radioresistance in breast cancer and its intervention strategies.Frontiers in immunology · 2026Pooled it
- Targeting lactylation in hepatocellular carcinoma: Mechanistic insights and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- Lactate dynamics in Parkinson's disease: striatal circuit vulnerability, biomarker potential, and therapeutic windows.Molecular medicine (Cambridge, Mass.) · 2026Review
- Targeting the Warburg Effect in Anaplastic Thyroid Carcinoma: Metabolic Vulnerabilities and Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Why Targeting Tumor Acidity Fails: Translational Barriers and Emerging Solutions.International journal of molecular sciences · 2026Review
- Obesity-derived metabolites modulate anti-tumor immunity in the tumor microenvironment: from mechanisms to clinical applications.BMC medicine · 2026Review
- Deciphering autophagy-metabolism interactions in cancer drug resistance: a comprehensive review.Cancer chemotherapy and pharmacology · 2026Review
- Lactate-lactylation in tumor angiogenesis and progression: mechanisms, biomarker potential, and therapeutic implications.Biomarker research · 2026Review
- Lactylation in cancer: molecular mechanisms and advances in clinical study.Molecular cancer · 2026Review
- The tumor microenvironment in leukemia: molecular pathways of immune evasion.Frontiers in immunology · 2026Review
- Dual roles of lactate and lactylation modification in the nervous system: neuroprotection and neuroinjury.Frontiers in aging neuroscience · 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
- Review
- Protein lactylation and immunotherapy in gliomas: A novel regulatory axis in tumor metabolism (Review).International journal of oncology · 2025Review
- Burning lactic acid: a road to revitalizing antitumor immunity.Frontiers of medicine · 2025Review
- Article
- Lactate metabolism and lactylation in breast cancer: mechanisms and implications.Cancer metastasis reviews · 2025Review
- Tumor microenvironment: recent advances in understanding and its role in modulating cancer therapies.Medical oncology (Northwood, London, England) · 2025Review
- L- and D-Lactate: unveiling their hidden functions in disease and health.Cell communication and signaling : CCS · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
To survive and proliferate in solid tumors, cancer cells adapt and evolve rapidly in microenvironments where oxygen and substrate bioavailability fluctuates over time and space. This creates metabolic heterogeneity. Cancer cells can further cooperate metabolically, for example by swapping glycolytic end-product lactate for blood-borne glucose. This type of cooperation can be targeted therapeutically, since transmembrane lactate exchanges are facilitated by lactate-proton symporters of the monocarboxylate (MCT) family. Among new drugs, AZD3965 is a first-in-class selective MCT1 inhibitor currently tested in Phase I/II clinical trials for patients with different types of cancers. Because MCT1 can function bidirectionally, we tested here whether and how malignant and nonmalignant cells adapt their metabolism and MCT repertoire when AZD3965 inhibits either lactate import or export. Using breast-associated malignant and nonmalignant cell lines as models, we report that AZD3965 is not directly cytotoxic. In the presence of glucose and glutamine, oxidative cells can survive when lactate uptake is blocked, and proliferating cells compensate MCT1 inhibition by overexpressing MCT4, a specialized facilitator of lactate export. Phenotypic characterization of mice focusing on metabolism, muscle and brain physiology found partial and transient memory retention defect as sole consequence of MCT1 inhibition by AZD3965. We therefore conclude that AZD3965 is compatible with anticancer 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.