ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Activity of the monocarboxylate transporter 1 inhibitor AZD3965 in small cell lung cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 236 papers, 4 of them syntheses that pooled it.
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Who cites it
236 citing papers in PubMed, 4 syntheses or guidelines pooled it, 348 citations in OpenAlex.
- Metabolomics and metabolites in cancer diagnosis and treatment.Molecular biomedicine · 2025Pooled it
- Prognostic Value of Monocarboxylate Transporter 1 Overexpression in Cancer: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- In Vivo Anticancer Activity of AZD3965: A Systematic Review.Molecules (Basel, Switzerland) · 2021Pooled it
- HPV, tumour metabolism and novel target identification in head and neck squamous cell carcinoma.British journal of cancer · 2019Pooled it
- mRNA Network: Solution for Tracking Chemotherapy Insensitivity in Small-Cell Lung Cancer.Journal of healthcare engineering · 2021Trial
- The MYBL2-GTSE1 axis promotes laryngeal squamous cell carcinoma progression by regulating PI3K/AKT-dependent glycolytic reprogramming.Cancer biology & therapy · 2026Article
- Application and mechanistic research of novel therapeutic strategies in cisplatin-resistant small cell lung cancer.Annals of medicine · 2026Review
- Research progress on lactate metabolism in lung cancer: Tumorigenesis, drug resistance and clinical translation (Review).Oncology reports · 2026Review
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Lactic acid exposure alters lysophosphatidic acid receptor-mediated regulation of growth and motility in pancreatic cancer cells.Molecular and cellular biochemistry · 2026Article
- Review
- Epigenetics in lung cancer precision medicine: from bench to bedside-a narrative review.Translational lung cancer research · 2026Review
- Targeting the cancer metabolism-immunity interface: update and perspectives.Experimental hematology & oncology · 2026Review
- Clinical implications of lactylation modification in digestive system tumors (Review).Oncology letters · 2026Review
- MCT4 mediates hypoxia-induced extracellular lactate release from IPF fibroblasts.American journal of respiratory cell and molecular biology · 2026Article
- Lactic acid induces dendritic cell pyroptosis through MCT-1 to promote tumor immune evasion.Oncogene · 2026Article
- Glycolytic cancer-associated fibroblasts orchestrate metabolic remodeling in the tumor microenvironment.Journal of experimental & clinical cancer research : CR · 2026Review
- Lactate metabolism and lactylation in female reproductive diseases: From metabolic rewiring to biomarkers and translational therapeutics.Clinical and translational medicine · 2026Review
- Tumor-derived branched-chain α-keto acids activate Notch signaling in tumor-associated macrophages to limit immunity.Nature immunology · 2026Article
- Why Targeting Tumor Acidity Fails: Translational Barriers and Emerging Solutions.International journal of molecular sciences · 2026Review
176 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
purposeThe monocarboxylate transporter 1 (MCT1) inhibitor, AZD3965, is undergoing phase I evaluation in the United Kingdom. AZD3965 is proposed, via lactate transport modulation, to kill tumor cells reliant on glycolysis. We investigated the therapeutic potential of AZD3965 in small cell lung cancer (SCLC) seeking rationale for clinical testing in this disease and putative predictive biomarkers for trial use. EXPERIMENTAL
designAZD3965 sensitivity was determined for seven SCLC cell lines, in normoxia and hypoxia, and for a tumor xenograft model. Proof of mechanism was sought via changes in intracellular/tumor lactate. Expression of MCT1 and related transporter MCT4 was assessed by Western blot analysis. Drug resistance was investigated via MCT4 siRNAi and overexpression. The expression and clinical significance of MCT1 and MCT4 were explored in a tissue microarray (TMA) from 78 patients with SCLC.
resultsAZD3965 sensitivity varied in vitro and was highest in hypoxia. Resistance in hypoxia was associated with increased MCT4 expression. In vivo, AZD3965 reduced tumor growth and increased intratumor lactate. In the TMA, high MCT1 expression was associated with worse prognosis (P = 0.014). MCT1 and hypoxia marker CA IX expression in the absence of MCT4 was observed in 21% of SCLC tumors.
conclusionsThis study provides a rationale to test AZD3965 in patients with SCLC. Our results suggest that patients with tumors expressing MCT1 and lacking in MCT4 are most likely to respond.
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