ArticleCellular oncology (Dordrecht, Netherlands)2011
Gamma-secretase inhibitor enhances the cytotoxic effect of bortezomib in multiple myeloma.
Article in Cellular oncology (Dordrecht, Netherlands), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Repurposing nirogacestat, a gamma secretase enzyme inhibitor in desmoid tumors.Future oncology (London, England) · 2025Review
- Updates on CAR T cell therapy in multiple myeloma.Biomarker research · 2024Review
- The critical role of γ-secretase and its inhibitors in cancer and cancer therapeutics.International journal of biological sciences · 2023Review
- Altered pathways and targeted therapy in double hit lymphoma.Journal of hematology & oncology · 2022Review
- Targeting Notch Inhibitors to the Myeloma Bone Marrow Niche Decreases Tumor Growth and Bone Destruction without Gut Toxicity.Cancer research · 2021Article
- Gamma Secretase Inhibitors in Cancer: A Current Perspective on Clinical Performance.The oncologist · 2021Review
- Cancer Stem Cells,Cells · 2020Review
- Targeting Notch signalling pathway of cancer stem cells.Stem cell investigation · 2018Review
- The γ-secretase inhibitors enhance the anti-leukemic activity of ibrutinib in B-CLL cells.Oncotarget · 2017Article
- [Clinical significance of S100A6 and Notch1 in multiple myeloma patients].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2017Article
- Multiple myeloma-derived Jagged ligands increases autocrine and paracrine interleukin-6 expression in bone marrow niche.Oncotarget · 2016Article
- Anti-myeloma effect of pharmacological inhibition of Notch/gamma-secretase with RO4929097 is mediated by modulation of tumor microenvironment.Cancer biology & therapy · 2016Article
- Cancer stem cells are the cause of drug resistance in multiple myeloma: fact or fiction?Oncotarget · 2015Review
- Targeting Notch1 and proteasome as an effective strategy to suppress T-cell lymphoproliferative neoplasms.Oncotarget · 2015Article
- Article
- Modulatory effects of bortezomib on host immune cell functions.Immunotherapy · 2015Review
- Notch signaling drives multiple myeloma induced osteoclastogenesis.Oncotarget · 2014Article
- Multiple myeloma mesenchymal stromal cells: Contribution to myeloma bone disease and therapeutics.World journal of stem cells · 2014Review
- Notch pathway inhibition controls myeloma bone disease in the murine MOPC315.BM model.Blood cancer journal · 2014Article
- Anti-Notch treatment prevents multiple myeloma cells localization to the bone marrow via the chemokine system CXCR4/SDF-1.Leukemia · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundTargeting of Notch signaling with γ-secretase inhibitors (GSIs) has been considered a promising strategy for the treatment of hematological malignancies including multiple myeloma (MM). Here we investigated whether the cytotoxic effect of bortezomib, an agent commonly used in MM, could be enhanced by the addition of a GSI.
methodsMM cells were treated with GSI, bortezomib or the combination thereof. Apoptosis of MM cells, proteasome activity and Notch signaling activation were determined. The effect of the drug combination was also evaluated in MM cells transfected with the active domain of Notch-1.
resultsUsing MM cell lines and primary MM cells isolated from the bone marrow of patients with MM we found a strong synergistic effect of bortezomib in combination with one of the GSIs studied. We next investigated the mechanism underlying this synergistic effect and determined that the effect of the drug combination was mainly dependent on the ability of the selected GSI to inhibit proteasome activity in MM cells.
conclusionOur study demonstrates that selected GSIs that inhibit proteasome activity may be successfully used in combination with bortezomib enhancing its anti-MM effect.
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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.