ArticleOncotarget2014
Hypoxia inducible factor-1 alpha as a therapeutic target in multiple myeloma.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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.
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.
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Who cites it
36 citing papers in PubMed.
- 3D biomimetic microgel platform for multiple myeloma: Approaching tumor microenvironment on cell lines and patient-derived cells.Materials today. Bio · 2026Article
- The role of antioxidants in multiple myeloma: diagnostic, prognostic, and therapeutic applications: a narrative review.Therapeutic advances in hematology · 2026Review
- Artificial blood-hope and the challenges to combat tumor hypoxia for anti-cancer therapy.Medical & biological engineering & computing · 2025Review
- New horizons in our understanding of precursor multiple myeloma and early interception.Nature reviews. Cancer · 2024Review
- Pathways to therapy resistance: The sheltering effect of the bone marrow microenvironment to multiple myeloma cells.Heliyon · 2024Review
- High levels of CRBN isoform lacking IMiDs binding domain predicts for a worse response to IMiDs-based upfront therapy in newly diagnosed myeloma patients.Clinical and experimental medicine · 2023Article
- Metabolic Alterations in Multiple Myeloma: From Oncogenesis to Proteasome Inhibitor Resistance.Cancers · 2023Review
- Shutting off the fuel supply to target metabolic vulnerabilities in multiple myeloma.Frontiers in oncology · 2023Review
- Hypoxia-Inducible Factor-1: A Novel Therapeutic Target for the Management of Cancer, Drug Resistance, and Cancer-Related Pain.Cancers · 2022Review
- HIF-1α Expression Increases Preoperative Concurrent Chemoradiotherapy Resistance in Hyperglycemic Rectal Cancer.Cancers · 2022Article
- Isotype-specific plasma cells express divergent transcriptional programs.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Review
- Clonal and subclonal TP53 molecular impairment is associated with prognosis and progression in multiple myeloma.Blood cancer journal · 2022Article
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- Role of hypoxia in inhibiting dendritic cells by VEGF signaling in tumor microenvironments: mechanism and application.American journal of cancer research · 2021Review
- Cytosolic serine hydroxymethyltransferase controls lung adenocarcinoma cells migratory ability by modulating AMP kinase activity.Cell death & disease · 2020Article
- Targeting the Endothelin-1 Receptors Curtails Tumor Growth and Angiogenesis in Multiple Myeloma.Frontiers in oncology · 2020Article
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The increasing importance of hypoxia-inducible factor-1α (HIF-1α) in tumorigenesis raises the possibility that agents which specifically inhibit this transcription factor, would provide significant therapeutic benefit. The constitutive expression of HIF-1α in about 35% of Multiple Myeloma (MM) patients suggests HIF-1α suppression might be part of a therapeutic strategy. Accordingly, we explored the effect of EZN-2968, a small 3rd generation antisense oligonucleotide against HIF-1α, in a panel of MM cell lines and primary patients samples. Here, we demonstrated that EZN-2968 is highly specific for HIF-1α mRNA and that exposure of MM cells to EZN-2968 resulted in an efficient and homogeneous loading of the cells showing a long lasting low HIF-1α protein level. In MM cells, HIF-1α suppression induced a permanent cell cycle arrest by prolonging S-phase through cyclin A modulation and in addition it induced a mild apoptotic cell death. Moreover, HIF-1α suppression caused a metabolic shift that leaded to increased production of ATP by oxidative phosphorylation (i.e. Warburg effect reversion), that was confirmed by the observed mitochondrial membrane potential decrease. These results show that HIF-1α is an important player in MM homeostasis and that its inhibition by small antisense oligonucleotides provides a rationale for novel therapeutic strategy to improving MM treatment.
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Registered trials
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