ArticleMolecular cancer therapeutics2013
Profiling bortezomib resistance identifies secondary therapies in a mouse myeloma model.
Article in Molecular cancer therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 78 citations in OpenAlex.
- Panobinostat PK/PD profile in combination with bortezomib and dexamethasone in patients with relapsed and relapsed/refractory multiple myeloma.European journal of clinical pharmacology · 2016Trial
- Epigenome-Wide Association Studies of Proteasome Inhibitor-Related Cardiotoxicity in Patients with Multiple Myeloma.Cancers · 2026Article
- A bortezomib resistance-related gene signature predicts prognosis, with ARID5B downregulation associated with poor overall survival in multiple myeloma.Discover oncology · 2026Article
- Impact of proteostasis workload on sensitivity to proteasome inhibitors in multiple myeloma.Clinical and experimental medicine · 2025Review
- Autophagy and Apoptosis: Current Challenges of Treatment and Drug Resistance in Multiple Myeloma.International journal of molecular sciences · 2022Review
- Epigenetic Crosstalk between Malignant Plasma Cells and the Tumour Microenvironment in Multiple Myeloma.Cancers · 2022Review
- Understanding Drug Sensitivity and Tackling Resistance in Cancer.Cancer research · 2022Article
- Adhesion molecules in multiple myeloma oncogenesis and targeted therapy.International journal of hematologic oncology · 2022Review
- secDrug: a pipeline to discover novel drug combinations to kill drug-resistant multiple myeloma cells using a greedy set cover algorithm and single-cell multi-omics.Blood cancer journal · 2022Article
- Drug resistance and minimal residual disease in multiple myeloma.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- RNA-Sequencing-Based Transcriptomic Score with Prognostic and Theranostic Values in Multiple Myeloma.Journal of personalized medicine · 2021Article
- Pathophysiological roles of myristoylated alanine-rich C-kinase substrate (MARCKS) in hematological malignancies.Biomarker research · 2021Review
- Review
- In vitro and ex vivo gene expression profiling reveals differential kinetic response of HSPs and UPR genes is associated with PI resistance in multiple myeloma.Blood cancer journal · 2020Article
- Preclinical validation of Alpha-Enolase (ENO1) as a novel immunometabolic target in multiple myeloma.Oncogene · 2020Article
- Tuning isoform selectivity and bortezomib sensitivity with a new class of alkenyl indene PDI inhibitor.European journal of medicinal chemistry · 2020Article
- The Nrf2/PGC1Oxidative medicine and cellular longevity · 2020Article
- Syrbactin proteasome inhibitor TIR-199 overcomes bortezomib chemoresistance and inhibits multiple myeloma tumor growth in vivo.Leukemia research · 2020Article
- E3 ubiquitin ligases in B-cell malignancies.Cellular immunology · 2019Review
- Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Multiple myeloma is a hematologic malignancy characterized by the proliferation of neoplastic plasma cells in the bone marrow. Although the first-to-market proteasome inhibitor bortezomib (Velcade) has been successfully used to treat patients with myeloma, drug resistance remains an emerging problem. In this study, we identify signatures of bortezomib sensitivity and resistance by gene expression profiling (GEP) using pairs of bortezomib-sensitive (BzS) and bortezomib-resistant (BzR) cell lines created from the Bcl-XL/Myc double-transgenic mouse model of multiple myeloma. Notably, these BzR cell lines show cross-resistance to the next-generation proteasome inhibitors, MLN2238 and carfilzomib (Kyprolis) but not to other antimyeloma drugs. We further characterized the response to bortezomib using the Connectivity Map database, revealing a differential response between these cell lines to histone deacetylase (HDAC) inhibitors. Furthermore, in vivo experiments using the HDAC inhibitor panobinostat confirmed that the predicted responder showed increased sensitivity to HDAC inhibitors in the BzR line. These findings show that GEP may be used to document bortezomib resistance in myeloma cells and predict individual sensitivity to other drug classes. Finally, these data reveal complex heterogeneity within multiple myeloma and suggest that resistance to one drug class reprograms resistant clones for increased sensitivity to a distinct class of drugs. This study represents an important next step in translating pharmacogenomic profiling and may be useful for understanding personalized pharmacotherapy for patients with multiple myeloma.
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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.