ArticlePloS one2015
Modulation of cell metabolic pathways and oxidative stress signaling contribute to acquired melphalan resistance in multiple myeloma cells.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
What it found
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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
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Can Targeting Hypoxia-Mediated Acidification of the Bone Marrow Microenvironment Kill Myeloma Tumor Cells?Frontiers in oncology · 2021Pooled it
- Trial
- <p>Regulatory networks of HIFs in tumor‑infiltrating immune cells: From molecular mechanisms to therapeutic implications (Review)</p>.International journal of oncology · 2026Review
- DNA Damage Response and Redox Status in the Resistance of Multiple Myeloma Cells to Genotoxic Treatment.International journal of molecular sciences · 2025Article
- Nucleic acid aptamers in orthopedic diseases: promising therapeutic agents for bone disorders.Bone research · 2025Review
- The Gene Expression Profile of Milk Somatic Cells of Small Ruminant Lentivirus-Seropositive and -Seronegative Dairy Goats (Viruses · 2025Article
- Unraveling Obesity and Multiple Myeloma: Insights from Epidemiology and Molecular Mechanisms.Current obesity reports · 2025Review
- Article
- MicroRNA-665 and its potential role in drug response and survival outcomes in multiple myeloma: a preliminary study.Frontiers in pharmacology · 2025Article
- L-Sarcolysine Reduced the Mobility of Human Glioblastoma Cells, with Potential Involvement of Vimentin.OncoTargets and therapy · 2025Article
- Metal Peroxide Nanoparticles for Modulating the Tumor Microenvironment: Current Status and Recent Prospects.Cancers · 2024Review
- Progression of monoclonal gammopathy of undetermined significance to multiple myeloma is associated with enhanced translational quality control and overall loss of surface antigens.Journal of translational medicine · 2024Article
- A proteomic landscape of pharmacologic perturbations for functional relevance.Journal of pharmaceutical analysis · 2024Article
- CDK7 controls E2F- and MYC-driven proliferative and metabolic vulnerabilities in multiple myeloma.Blood · 2023Article
- AKT supports the metabolic fitness of multiple myeloma cells by restricting FOXO activity.Blood advances · 2023Article
- Deregulated Metabolic Pathways in Ovarian Cancer: Cause and Consequence.Metabolites · 2023Review
- Hypoxia-responsive circular RNA circAAGAB reduces breast cancer malignancy by activating p38 MAPK and sponging miR-378 h.Cancer cell international · 2023Article
- Targeting the βThe Journal of pathology · 2023Article
- Rewiring of mitochondrial metabolism in therapy-resistant cancers: permanent and plastic adaptations.Frontiers in cell and developmental biology · 2023Review
- A novel glycolysis-related gene signature for predicting the prognosis of multiple myeloma.Frontiers in cell and developmental biology · 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
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alkylating agents are widely used chemotherapeutics in the treatment of many cancers, including leukemia, lymphoma, multiple myeloma, sarcoma, lung, breast and ovarian cancer. Melphalan is the most commonly used chemotherapeutic agent against multiple myeloma. However, despite a 70-80% initial response rate, virtually all patients eventually relapse due to the emergence of drug-resistant tumour cells. By using global proteomic and transcriptomic profiling on melphalan sensitive and resistant RPMI8226 cell lines followed by functional assays, we discovered changes in cellular processes and pathways not previously associated with melphalan resistance in multiple myeloma cells, including a metabolic switch conforming to the Warburg effect (aerobic glycolysis), and an elevated oxidative stress response mediated by VEGF/IL8-signaling. In addition, up-regulated aldo-keto reductase levels of the AKR1C family involved in prostaglandin synthesis contribute to the resistant phenotype. Finally, selected metabolic and oxidative stress response enzymes were targeted by inhibitors, several of which displayed a selective cytotoxicity against the melphalan-resistant cells and should be further explored to elucidate their potential to overcome melphalan resistance.
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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.