ArticleThe Journal of clinical investigation2018
Inhibition of the aryl hydrocarbon receptor/polyamine biosynthesis axis suppresses multiple myeloma.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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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.
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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
39 citing papers in PubMed, 53 citations in OpenAlex.
- Different endurance exercises modulate NK cell cytotoxic and inhibiting receptors.European journal of applied physiology · 2021Trial
- Review
- Aryl hydrocarbon receptor pharmacology-mechanisms, ligands, and therapeutic potential.Pharmacological reviews · 2026Review
- Environmental exposures and multiple myeloma risk: A contemporary review of epidemiologic associations and mechanistic plausibility.Blood reviews · 2026Review
- The gut microbiota-aromatic amino acid axis in cardiovascular disease: pathophysiological roles, translational biomarkers, and therapeutic targeting.Frontiers in cardiovascular medicine · 2026Review
- Why are long-lived plasma cells long-lived?Frontiers in immunology · 2026Review
- Article
- Therapeutic resistance and combination therapy for cancer: recent developments and future directions.Scientific reports · 2025Article
- Polyamine metabolism and anti-tumor immunity.Frontiers in immunology · 2025Review
- Clofazimine inhibits small-cell lung cancer progression by modulating the kynurenine/aryl hydrocarbon receptor axis.International journal of biological macromolecules · 2024Article
- Review
- Clinical drug screening reveals clofazimine potentiates the efficacy while reducing the toxicity of anti-PD-1 and CTLA-4 immunotherapy.Cancer cell · 2024Article
- Aryl hydrocarbon receptor suppresses STING-mediated type I IFN expression in triple-negative breast cancer.Scientific reports · 2024Article
- The aryl hydrocarbon receptor as a tumor modulator: mechanisms to therapy.Frontiers in oncology · 2024Review
- Aryl hydrocarbon receptor confers protection against macrophage pyroptosis and intestinal inflammation through regulating polyamine biosynthesis.Theranostics · 2024Article
- Betacoronaviruses SARS-CoV-2 and HCoV-OC43 infections in IGROV-1 cell line require aryl hydrocarbon receptor.Emerging microbes & infections · 2023Article
- Aryl hydrocarbon receptor is a tumor promoter iniScience · 2023Article
- Non-Toxicological Role of Aryl Hydrocarbon Receptor in Obesity-Associated Multiple Myeloma Cell Growth and Survival.Cancers · 2023Article
- Monoterpenoid aryl hydrocarbon receptor allosteric antagonists protect against ultraviolet skin damage in female mice.Nature communications · 2023Article
- JAZF1: A Metabolic Regulator of Sensitivity to a Polyamine-Targeted Therapy.Molecular cancer research : MCR · 2023Article
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Authors and funding
24 authors at 3 institutions in 1 country.
Funding
Abstract
Polyamine inhibition for cancer therapy is, conceptually, an attractive approach but has yet to meet success in the clinical setting. The aryl hydrocarbon receptor (AHR) is the central transcriptional regulator of the xenobiotic response. Our study revealed that AHR also positively regulates intracellular polyamine production via direct transcriptional activation of 2 genes, ODC1 and AZIN1, which are involved in polyamine biosynthesis and control, respectively. In patients with multiple myeloma (MM), AHR levels were inversely correlated with survival, suggesting that AHR inhibition may be beneficial for the treatment of this disease. We identified clofazimine (CLF), an FDA-approved anti-leprosy drug, as a potent AHR antagonist and a suppressor of polyamine biosynthesis. Experiments in a transgenic model of MM (Vk*Myc mice) and in immunocompromised mice bearing MM cell xenografts revealed high efficacy of CLF comparable to that of bortezomib, a first-in-class proteasome inhibitor used for the treatment of MM. This study identifies a previously unrecognized regulatory axis between AHR and polyamine metabolism and reveals CLF as an inhibitor of AHR and a potentially clinically relevant anti-MM agent.
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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.