ArticleBlood advances2023
SUMOylation inhibition overcomes proteasome inhibitor resistance in multiple myeloma.
Article in Blood advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Drug Resistance in Multiple Myeloma: Tumor-Intrinsic Mechanisms and the Bone Marrow Microenvironment.Cell biochemistry and function · 2026Review
- UBA2: the gatekeeper of the sumoylation pathway and its multifaceted roles in human diseases and therapeutic prospects.Clinical and experimental medicine · 2026Review
- Importance of SUMOylation Consensus Sequence of MAFK in Regulating EMT, Tumor Growth, Stemness, and Drug Resistance.Cancer science · 2026Article
- Beyond Bonferroni: new multiple contrast tests for time-to-event data under non-proportional hazards.Lifetime data analysis · 2026Article
- ZNF184-mediated transcriptional activation of SAE1 drives the cell cycle entry and immune evasion in non-small cell lung cancer.Respiratory research · 2025Article
- Immune regulation by the SUMO family.Nature reviews. Immunology · 2025Review
- Inhibition of CDC27 O-GlcNAcylation coordinates the antitumor efficacy in multiple myeloma through the autophagy-lysosome pathway.Acta pharmacologica Sinica · 2025Article
- SUMOylation facilitates the stability of BCR-ABL to promote chronic myeloid leukemia progression.Oncogene · 2025Article
- Post-Translational Modifications in Multiple Myeloma: Mechanisms of Drug Resistance and Therapeutic Opportunities.Biomolecules · 2025Review
- SENP3 inhibition suppresses hepatocellular carcinoma progression and improves the efficacy of anti-PD-1 immunotherapy.Cell death and differentiation · 2025Article
- Post-translational modifications orchestrate mTOR-driven cell death in cardiovascular disease.Frontiers in cardiovascular medicine · 2025Review
- Integrated machine learning and single-cell analysis reveal the prognostic and therapeutic potential of SUMOylation-related genes in ovarian cancer.Frontiers in immunology · 2025Article
- The SUMO Family: Mechanisms and Implications in Thyroid Cancer Pathogenesis and Therapy.Biomedicines · 2024Review
- Targeted inhibition of SUMOylation: treatment of tumors.Human cell · 2024Review
- Proteasome and PARP1 dual-target inhibitor for multiple myeloma: Fluzoparib.Biochemistry and biophysics reports · 2024Article
- The prognostic significance of ubiquitination-related genes in multiple myeloma by bioinformatics analysis.BMC medical genomics · 2024Article
- MUC20 regulated by extrachromosomal circular DNA attenuates proteasome inhibitor resistance of multiple myeloma by modulating cuproptosis.Journal of experimental & clinical cancer research : CR · 2024Article
- Paradoxes of Cellular SUMOylation Regulation: A Role of Biomolecular Condensates?Pharmacological reviews · 2023Review
- SAE1 May Play a Pro-Carcinogenic Role in Pancreatic Adenocarcinoma: A Comprehensive Study Integrating Multiple Pieces of Evidence.IET systems biologyArticle
Corrections and comments
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Authors and funding
25 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteasome inhibition is a highly effective treatment for multiple myeloma (MM). However, virtually all patients develop proteasome inhibitor resistance, which is associated with a poor prognosis. Hyperactive small ubiquitin-like modifier (SUMO) signaling is involved in both cancer pathogenesis and cancer progression. A state of increased SUMOylation has been associated with aggressive cancer biology. We found that relapsed/refractory MM is characterized by a SUMO-high state, and high expression of the SUMO E1-activating enzyme (SAE1/UBA2) is associated with poor overall survival. Consistently, continuous treatment of MM cell lines with carfilzomib (CFZ) enhanced SUMO pathway activity. Treatment of MM cell lines with the SUMO E1-activating enzyme inhibitor subasumstat (TAK-981) showed synergy with CFZ in both CFZ-sensitive and CFZ-resistant MM cell lines, irrespective of the TP53 state. Combination therapy was effective in primary MM cells and in 2 murine MM xenograft models. Mechanistically, combination treatment with subasumstat and CFZ enhanced genotoxic and proteotoxic stress, and induced apoptosis was associated with activity of the prolyl isomerase PIN1. In summary, our findings reveal activated SUMOylation as a therapeutic target in MM and point to combined SUMO/proteasome inhibition as a novel and potent strategy for the treatment of proteasome inhibitor-resistant MM.
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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.