ArticleCancer & metabolism2017
Bortezomib resistance in multiple myeloma is associated with increased serine synthesis.
Article in Cancer & metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
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Who cites it
108 citing papers in PubMed, 185 citations in OpenAlex.
- N-Acetylornithine Depletion in Bone Marrow Biopsy: A Novel Microenvironment-Specific Hallmark for Multiple Myeloma Diagnosis.International journal of laboratory hematology · 2026Article
- Pristimerin Suppresses Janus Kinase/Signal Transducers and Activators of Transcription Oncogenic Signaling To Drive Mitochondrial and Caspase-Dependent Apoptosis in Multiple Myeloma.ACS pharmacology & translational science · 2026Article
- Extracellular Enolase-1 Promotes CAF-Associated Stromal Reprogramming via the Plasmin/TGF-β Axis in Multiple Myeloma.Cancers · 2026Article
- Small molecule screening identifies cytotoxic endoplasmic reticulum-associated degradation inhibitors in multiple myeloma.Cell death & disease · 2026Article
- The role of antioxidants in multiple myeloma: diagnostic, prognostic, and therapeutic applications: a narrative review.Therapeutic advances in hematology · 2026Review
- Nutritional approaches in combating therapeutic resistance and enhancing treatment efficacy in cancer: the impact of ketogenic diets.Nutrition & metabolism · 2025Review
- TRIP13 alters mitochondrial function and promotes bortezomib resistance in multiple myeloma.Scientific reports · 2025Article
- Article
- Carfilzomib resistance in multiple myeloma: A comparative metabolomic analysis.Journal of applied genetics · 2025Article
- Targeting the crosstalk of metabolism reprogramming and replication stress: novel strategy to combat cancer.Medical oncology (Northwood, London, England) · 2025Review
- Spatiotemporal Heterogeneity of Tumor Glucose Metabolism Reprogramming: From Single-Cell Mechanisms to Precision Interventions.International journal of molecular sciences · 2025Review
- PHGDH drives 5-FU chemoresistance in colorectal cancer through the Hedgehog signaling.Journal of experimental & clinical cancer research : CR · 2025Article
- Inhibition of CDC27 O-GlcNAcylation coordinates the antitumor efficacy in multiple myeloma through the autophagy-lysosome pathway.Acta pharmacologica Sinica · 2025Article
- Enhancing plasmacytoid dendritic cell functionality withMolecular therapy. Oncology · 2025Article
- The oligosaccharyltransferase complex is an essential component of multiple myeloma plasma cells.Molecular therapy. Oncology · 2025Article
- Impact of immune cell metabolism on membranous nephropathy and prospective therapy.Communications biology · 2025Review
- Metabolic reprogramming induced by PSMA4 overexpression facilitates bortezomib resistance in multiple myeloma.Annals of hematology · 2025Article
- Metabolic profiling of patient-derived organoids reveals nucleotide synthesis as a metabolic vulnerability in malignant rhabdoid tumors.Cell reports. Medicine · 2025Article
- FOXC1-mediated serine metabolism reprogramming enhances colorectal cancer growth and 5-FU resistance under serine restriction.Cell communication and signaling : CCS · 2025Article
- Stable Isotope Tracing Experiments Using LC-MS.Methods in molecular biology (Clifton, N.J.) · 2025Article
48 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe proteasome inhibitor bortezomib (BTZ) is successfully applied in the treatment of multiple myeloma, but its efficacy is restricted by the wide-spread occurrence of resistance. Metabolic alterations play an important role in cancer development and aid in the cellular adaptation to pharmacologically changed environments. Metabolic changes could therefore play an essential role in the development of drug resistance. However, specific metabolic pathways that can be targeted to improve bortezomib therapy remain unidentified.
methodsWe elucidated the metabolic mechanisms underlying bortezomib resistance by using mass spectrometry-based metabolomics and proteomics on BTZ-sensitive and BTZ-resistant multiple myeloma cell lines as well as in a set of CD138+ cells obtained from multiple myeloma patients.
resultsOur findings demonstrate that a rewired glucose metabolism sustains bortezomib resistance. Mechanistically, this results in higher activity of both the pentose phosphate pathway and serine synthesis pathway, ultimately leading to an increased anti-oxidant capacity of BTZ-resistant cells. Moreover, our results link both serine synthesis pathway activity and expression of 3-phosphoglycerate dehydrogenase (PHGDH), which catalyzes the rate-limiting step of serine synthesis, to bortezomib resistance across different BTZ-resistant multiple myeloma cell lines. Consistently, serine starvation enhanced the cytotoxicity of bortezomib, underscoring the importance of serine metabolism in the response to BTZ. Importantly, in CD138+ cells of clinically bortezomib refractory multiple myeloma patients, PHGDH expression was also markedly increased.
conclusionsOur findings indicate that interfering with serine metabolism may be a novel strategy to improve bortezomib therapy and identify PHGDH as a potential biomarker for BTZ resistance.
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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.