ArticleOncotarget2015
Harnessing Noxa demethylation to overcome Bortezomib resistance in mantle cell lymphoma.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
11 citing papers in PubMed, 17 citations in OpenAlex.
- Ubiquitin proteasome system (UPS): a crucial determinant of the epigenetic landscape in cancer.Epigenomics · 2025Review
- Article
- Review
- 5-Aza-2'-Deoxycytidine Alters the Methylation Profile of Bortezomib-Resistant U266 Multiple Myeloma Cells and Affects Their Proliferative Potential.International journal of molecular sciences · 2023Article
- TAZ functions as a tumor suppressor in multiple myeloma by downregulating MYC.Blood advances · 2019Article
- Cyclin D1-CDK4 activity drives sensitivity to bortezomib in mantle cell lymphoma by blocking autophagy-mediated proteolysis of NOXA.Journal of hematology & oncology · 2018Article
- The preclinical discovery and development of bortezomib for the treatment of mantle cell lymphoma.Expert opinion on drug discovery · 2017Review
- Bortezomib-resistance is associated with increased levels of proteasome subunits and apoptosis-avoidance.Oncotarget · 2016Article
- Mantle cell lymphoma in the era of precision medicine-diagnosis, biomarkers and therapeutic agents.Oncotarget · 2016Review
- Epigenetics: A primer for clinicians.Blood reviews · 2016Review
- Bortezomib inhibits Burkitt's lymphoma cell proliferation by downregulating sumoylated hnRNP K and c-Myc expression.Oncotarget · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
Bortezomib (BZM) is the first proteasome inhibitor approved for relapsed Mantle Cell Lymphoma (MCL) with durable responses seen in 30%-50% of patients. Given that a large proportion of patients will not respond, BZM resistance is a significant barrier to use this agent in MCL. We hypothesized that a subset of aberrantly methylated genes may be modulating BZM response in MCL patients. Genome-wide DNA methylation analysis using a NimbleGen array platform revealed a striking promoter hypomethylation in MCL patient samples following BZM treatment. Pathway analysis of differentially methylated genes identified molecular mechanisms of cancer as a top canonical pathway enriched among hypomethylated genes in BZM treated samples. Noxa, a pro-apoptotic Bcl-2 family member essential for the cytotoxicity of BZM, was significantly hypomethylated and induced following BZM treatment. Therapeutically, we could demethylate Noxa and induce anti-lymphoma activity using BZM and the DNA methytransferase inhibitor Decitabine (DAC) and their combination in vitro and in vivo in BZM resistant MCL cells. These findings suggest a role for dynamic Noxa methylation for the therapeutic benefit of BZM. Potent and synergistic cytotoxicity between BZM and DAC in vitro and in vivo supports a strategy for using epigenetic priming to overcome BZM resistance in relapsed MCL patients.
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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.