ArticleOncotarget2017
Anthracyclines suppress pheochromocytoma cell characteristics, including metastasis, through inhibition of the hypoxia signaling pathway.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 36 citations in OpenAlex.
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- Hypoxia-inducible transcription factors: architects of tumorigenesis and targets for anticancer drug discovery.Transcription · 2025Review
- HIF-1 and HIF-2 in cancer: structure, regulation, and therapeutic prospects.Cellular and molecular life sciences : CMLS · 2025Review
- Regulation of Hypoxia Dependent Reprogramming of Cancer Metabolism: Role of HIF-1 and Its Potential Therapeutic Implications in Leukemia.Asian Pacific journal of cancer prevention : APJCP · 2024Review
- Tumor hypoxia and role of hypoxia-inducible factor in oral cancer.World journal of surgical oncology · 2024Review
- Proteomics analysis of carotid body tumor revealed potential mechanisms and molecular differences among Shamblin classifications.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Article
- Mechanisms involved in selecting and maintaining neuroblastoma cancer stem cell populations, and perspectives for therapeutic targeting.World journal of stem cells · 2021Review
- Cancer Cell Metabolism in Hypoxia: Role of HIF-1 as Key Regulator and Therapeutic Target.International journal of molecular sciences · 2021Review
- Hypoxia-Driven Effects in Cancer: Characterization, Mechanisms, and Therapeutic Implications.Cells · 2021Review
- Hypoxia-induced alternative splicing in human diseases: the pledge, the turn, and the prestige.Cellular and molecular life sciences : CMLS · 2021Review
- [Long non-coding RNA UPK1A-AS1 promotes glycolysis in hepatocellular carcinoma cellsNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021Article
- A Multi-Omics Study Revealing the Metabolic Effects of Estrogen in Liver Cancer Cells HepG2.Cells · 2021Article
- Review
- Circular RNA Circ-0003006 Promotes Hepatocellular Carcinoma Proliferation and Metastasis Through Sponging miR-542-3p and Regulating HIF-1A.Cancer management and research · 2021Article
- Emerging Treatments for Advanced/Metastatic Pheochromocytoma and Paraganglioma.Current treatment options in oncology · 2020Review
- Hypoxia-induced alternative splicing: the 11th Hallmark of Cancer.Journal of experimental & clinical cancer research : CR · 2020Review
- Targeting NRF2-Governed Glutathione Synthesis forCancers · 2020Article
- Association ofBioMed research international · 2020Article
- Review
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 3 countries.
Funding
Abstract
Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare, neuroendocrine tumors derived from adrenal or extra-adrenal chromaffin cells, respectively. Metastases are discovered in 3-36% of patients at the time of diagnosis. Currently, only suboptimal treatment options exist. Therefore, new therapeutic compounds targeting metastatic PHEOs/PGLs are urgently needed. Here, we investigated if anthracyclines were able to suppress the progression of metastatic PHEO. We explored their effects on experimental mouse PHEO tumor cells using in vitro and in vivo models, and demonstrated that anthracyclines, particularly idarubicin (IDA), suppressed hypoxia signaling by preventing the binding of hypoxia-inducible factor 1 and 2 (HIF-1 and HIF-2) to the hypoxia response element (HRE) sites on DNA. This resulted in reduced transcriptional activation of HIF target genes, including erythropoietin (EPO), phosphoglycerate kinase 1 (PGK1), endothelin 1 (EDN1), glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), and vascular endothelial growth factor (VEGFA), which consequently inhibited the growth of metastatic PHEO. Additionally, IDA downregulated hypoxia signaling by interfering with the transcriptional activation of HIF1A and HIF2A. Furthermore, our animal model demonstrated the dose-dependent suppressive effect of IDA on metastatic PHEO growth in vivo. Our results indicate that anthracyclines are prospective candidates for inclusion in metastatic PHEO/PGL therapy, especially in patients with gene mutations involved in the hypoxia signaling pathway.
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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.