ArticleBritish journal of cancer2021
Modulating proteasome inhibitor tolerance in multiple myeloma: an alternative strategy to reverse inevitable resistance.
Article in British journal of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- The Shape-Shifting Myeloma: Adaptive Plasticity as a Hallmark of Relapse and Refractoriness.Cancers · 2026Review
- Proteasome inhibition enhances lysosome-mediated targeted protein degradation.Cell death & disease · 2026Article
- Article
- Promoter hypomethylation drives ABCB1-mediated carfilzomib resistance in multiple myeloma.Clinical epigenetics · 2026Article
- Noncanonical role of KDM5C in conferring bortezomib resistance via the PERK‒Nrf2 axis in multiple myeloma.Cell death & disease · 2026Article
- Phosphoproteomic Profiling of Multiple Myeloma Based on Ex Vivo Drug Sensitivity Resistance Testing Identifies Phosphorylation Signatures Associated with Drug Response.Biomolecules · 2026Article
- Drug-tolerant persister cells: the deadly survivors in hematological malignancies.Frontiers in pharmacology · 2026Review
- DEK facilitates bortezomib resistance of multiple myeloma by modulating ferroptosis.Clinical and experimental medicine · 2025Article
- Investigating the role of tumor cell heterogeneity and angiogenesis genes in the prognosis of multiple myeloma.Frontiers in immunology · 2025Article
- Proteasome: Role in T Cell Function Regulation.International journal of biological sciences · 2025Review
- Interplay between proteasome inhibitors and NF-κB pathway in leukemia and lymphoma: a comprehensive review on challenges ahead of proteasome inhibitors.Cell communication and signaling : CCS · 2024Review
- Mechanism of selective recognition of Lys48-linked polyubiquitin by macrocyclic peptide inhibitors of proteasomal degradation.Nature communications · 2023Article
- Mass Spectrometry-Based Proteomics: Analyses Related to Drug-Resistance and Disease Biomarkers.Medicina (Kaunas, Lithuania) · 2023Review
- Lysin (K)-specific demethylase 1 inhibition enhances proteasome inhibitor response and overcomes drug resistance in multiple myeloma.Experimental hematology & oncology · 2023Article
- Deacetylation induced nuclear condensation of HP1γ promotes multiple myeloma drug resistance.Nature communications · 2023Article
- Dissecting and targeting noncanonical functions of EZH2 in multiple myeloma via an EZH2 degrader.Oncogene · 2023Article
- Dynamic single-cell RNA-seq analysis reveals distinct tumor program associated with microenvironmental remodeling and drug sensitivity in multiple myeloma.Cell & bioscience · 2023Article
- Review
- Review
- The aspartyl protease DDI2 drives adaptation to proteasome inhibition in multiple myeloma.Cell death & disease · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundResistance to proteasome inhibitors (PIs) is a major obstacle to the successful treatment of multiple myeloma (MM). Many mechanisms have been proposed for PI resistance; however, our mechanistic understanding of how PI resistance is inevitably acquired and reversed remains incomplete.
methodsMM patients after bortezomib relapse, MM cell lines and mouse models were used to generate matched resistant and reversed cells. RNA sequencing and bioinformatics analyses were employed to assess dysregulated epigenetic regulators. In vitro and in vivo procedures were used to characterise PI-tolerant cells and therapeutic efficacy.
resultsUpon PI treatment, MM cells enter a slow-cycling and reversible drug-tolerant state. This reversible phenotype is associated with epigenetic plasticity, which involves tolerance rather than persistence in patients with relapsed MM. Combination treatment with histone deacetylase inhibitors and high-dosage intermittent therapy, as opposed to sustained PI monotherapy, can be more effective in treating MM by preventing the emergence of PI-tolerant cells. The therapeutic basis is the reversal of dysregulated epigenetic regulators in MM patients.
conclusionsWe propose an alternative non-mutational PI resistance mechanism that explains why PI relapse is inevitable and why patients regain sensitivity after a 'drug holiday'. Our study also suggests strategies for epigenetic elimination of drug-tolerant cells.
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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.