ArticleOncotarget2015
The combination of HDAC and aminopeptidase inhibitors is highly synergistic in myeloma and leads to disruption of the NFκB signalling pathway.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 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
8 citing papers in PubMed, 11 citations in OpenAlex.
- Targeting EBV-associated gastric cancer by lytic induction therapy with nanatinostat.Tumour virus research · 2026Article
- Statins markedly potentiate aminopeptidase inhibitor activity against (drug-resistant) human acute myeloid leukemia cells.Cancer drug resistance (Alhambra, Calif.) · 2023Article
- Development of a Bestatin-SAHA Hybrid with Dual Inhibitory Activity against APN and HDAC.Molecules (Basel, Switzerland) · 2020Article
- Management of epigenomic networks entailed in coronavirus infections and COVID-19.Clinical epigenetics · 2020Review
- Review
- Integrated Assessment of Viral Transcription, Antigen Presentation, and CD8Journal of virology · 2020Article
- Epigenetic Modulators as Potential Multi-targeted Drugs Against Hedgehog Pathway for Treatment of Cancer.The protein journal · 2019Article
- Loss of CYLD expression unleashes Wnt signaling in multiple myeloma and is associated with aggressive disease.Oncogene · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
There is a growing body of evidence supporting the use of epigenetic therapies in the treatment of multiple myeloma. We show the novel HDAC inhibitor CHR-3996 induces apoptosis in myeloma cells at concentrations in the nanomolar range and with apoptosis mediated by p53 and caspase pathways. In addition, HDAC inhibitors are highly synergistic, both in vitro and in vivo, with the aminopeptidase inhibitor tosedostat (CHR-2797). We demonstrate that the basis for this synergy is a consequence of changes in the levels of NFκB regulators BIRC3/cIAP2, A20, CYLD, and IκB, which were markedly affected by the combination. When co-administered the HDAC and aminopeptidase inhibitors caused rapid nuclear translocation of NFκB family members p65 and p52, following activation of both canonical and non-canonical NFκB signalling pathways. The subsequent up-regulation of inhibitors of NFκB activation (most significantly BIRC3/cIAP2) turned off the cytoprotective effects of the NFκB signalling response in a negative feedback loop. These results provide a rationale for combining HDAC and aminopeptidase inhibitors clinically for the treatment of myeloma patients and support the disruption of the NFκB signalling pathway as a therapeutic strategy.
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What OpenQuestion holds
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.