ReviewCancer science2021
Impact of hypoxia on the pathogenesis and therapy resistance in multiple myeloma.
Review in Cancer science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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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
27 citing papers in PubMed, 33 citations in OpenAlex.
- CD70/CD27 signaling promotes the pathogenesis of multiple myeloma and represents a promising therapeutic target.Leukemia · 2026Article
- Coumarin- and Dipicolylamine-Terpenoid Hybrids as Selective Carbonic Anhydrases IX and XII Inhibitors: Mechanistic Insights and Selective Anti-Cancer Potential.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Oxidative Stress in Multiple Myeloma: Pathogenic Mechanisms, Biomarkers, and Redox-Targeted Therapeutic Strategies.International journal of molecular sciences · 2026Review
- Genomic profiling enables personalized strategies to overcome drug resistance in multiple myeloma.Discover oncology · 2026Review
- Mechanisms and intervention strategies of microenvironment-mediated drug resistance in multiple myeloma.Cancer cell international · 2026Review
- MMSA-1 is regulated by Wnt/TCF4 and involved in multiple myeloma progression and invasion via RAS/RAF signaling pathway.Annals of hematology · 2026Article
- Immunologic Combinations in Multiple Myeloma: Synergistic Stimulation with T cells and NK cells.International journal of biological sciences · 2026Review
- CAR-NK cell therapy in multiple myeloma: from preclinical and clinical landscape to joining the force for treatment strategies optimization.Cell communication and signaling : CCS · 2025Review
- Clusterin-mediated polarization of M2 macrophages: a mechanism of temozolomide resistance in glioblastoma stem cells.Stem cell research & therapy · 2025Article
- c-FOS Confers Stem Cell-like Features to Multiple Myeloma Cells in a Bone Marrow Microenvironment.Cells · 2025Article
- Article
- Adipocytes and metabolism: Contributions to multiple myeloma.Journal of bone oncology · 2024Article
- Exosomal miR-182 derived from bone marrow mesenchymal stem cells drives carfilzomib resistance of multiple myeloma cells by targeting SOX6.Journal of orthopaedic surgery and research · 2023Article
- Construction of Bone Hypoxic Microenvironment Based on Bone-on-a-Chip Platforms.International journal of molecular sciences · 2023Review
- Hypoxia-induced oxidative stress promotes therapy resistance via upregulation of heme oxygenase-1 in multiple myeloma.Cancer medicine · 2023Article
- Tumor cell plasticity in targeted therapy-induced resistance: mechanisms and new strategies.Signal transduction and targeted therapy · 2023Review
- Extracellular vesicles released during hypoxia transport heparanase and enhance macrophage migration, endothelial tube formation and cancer cell stemness.Proteoglycan research · 2023Article
- Effect of tumor microenvironment on ferroptosis: inhibition or promotion.Frontiers in oncology · 2023Review
- Autophagy-related mechanisms for treatment of multiple myeloma.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Crosstalk in the diseased plasma cell niche - the force of inflammation.Frontiers in immunology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple myeloma (MM) is a refractory plasma cell tumor. In myeloma cells, the transcription factor IRF4, the master regulator of plasma cells, is aberrantly upregulated and plays an essential role in oncogenesis. IRF4 forms a positive feedback loop with MYC, leading to additional tumorigenic properties. In recent years, molecular targeted therapies have contributed to a significant improvement in the prognosis of MM. Nevertheless, almost all patients experience disease progression, which is thought to be a result of treatment resistance induced by various elements of the bone marrow microenvironment. Among these, the hypoxic response, one of the key processes for cellular homeostasis, induces hypoxia-adapted traits such as undifferentiation, altered metabolism, and dissemination, leading to drug resistance. These inductions are caused by ectopic gene expression changes mediated by the activation of hypoxia-inducible factors (HIFs). By contrast, the expression levels of IRF4 and MYC are markedly reduced by hypoxic stress. Notably, an anti-apoptotic capability is usually acquired under both normoxic and hypoxic conditions, but the mechanism is distinct. This fact strongly suggests that myeloma cells may survive by switching their dependent regulatory factors from IRF4 and MYC (normoxic bone marrow region) to HIF (hypoxic bone marrow microenvironment). Therefore, to achieve deep remission, combination therapeutic agents, which are complementarily effective against both IRF4-MYC-dominant and HIF-dominated fractions, may become an important therapeutic strategy for MM.
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