ArticleCell cycle (Georgetown, Tex.)2015
Ibrutinib inhibits BTK-driven NF-κB p65 activity to overcome bortezomib-resistance in multiple myeloma.
Article in Cell cycle (Georgetown, Tex.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03702725 (A Phase I Study of Ibrutinib), which is not on this map. Cited by 30 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.
A Phase I Study of Ibrutinib (PCI-32765) in Combination With Revlimid/Dexamethasone (Rd) in Relapsed/Refractory Multiple Myeloma
Who cites it
30 citing papers in PubMed, 53 citations in OpenAlex.
- Decoding NF-κB: nucleocytoplasmic shuttling dynamics, synthetic modulation and post-therapeutic behavior in cancer.Molecular biology reports · 2025Review
- Ibrutinib in Combination with Lenalidomide Revlimid/Dexamethasone in Relapsed/Refractory Multiple Myeloma (AFT-15).Cancers · 2025Article
- Pathways to therapy resistance: The sheltering effect of the bone marrow microenvironment to multiple myeloma cells.Heliyon · 2024Review
- Article
- Autophagy: A Potential Therapeutic Target to Tackle Drug Resistance in Multiple Myeloma.International journal of molecular sciences · 2023Review
- Expression Modulation of Immune Checkpoint Molecules by Ibrutinib and Everolimus Through STAT3 in MCF-7 Breast Cancer Cells.Iranian journal of pharmaceutical research : IJPR · 2022Article
- Article
- The Mucolipin TRPML2 Channel Enhances the Sensitivity of Multiple Myeloma Cell Lines to Ibrutinib and/or Bortezomib Treatment.Biomolecules · 2022Article
- Inhibition of apoptosis-regulatory protein Siva-1 reverses multidrug resistance in gastric cancer by targeting PCBP1.Oncology research · 2022Article
- Development of a novel Bruton's tyrosine kinase inhibitor that exerts anti-cancer activities potentiates response of chemotherapeutic agents in multiple myeloma stem cell-like cells.Frontiers in pharmacology · 2022Article
- Autophagy and the Bone Marrow Microenvironment: A Review of Protective Factors in the Development and Maintenance of Multiple Myeloma.Frontiers in immunology · 2022Review
- Bruton's Tyrosine Kinase Targeting in Multiple Myeloma.International journal of molecular sciences · 2021Review
- Crosstalk between endoplasmic reticulum stress and oxidative stress: a dynamic duo in multiple myeloma.Cellular and molecular life sciences : CMLS · 2021Review
- Article
- The Landscape of Signaling Pathways and Proteasome Inhibitors Combinations in Multiple Myeloma.Cancers · 2021Review
- Emergence of overt myeloma in a patient with chronic lymphocytic leukemia on ibrutinib therapy.Clinical case reports · 2020Article
- LCRF-0006, a small molecule mimetic of the N-cadherin antagonist peptide ADH-1, synergistically increases multiple myeloma response to bortezomib.FASEB bioAdvances · 2020Article
- TLR4 signaling drives mesenchymal stromal cells commitment to promote tumor microenvironment transformation in multiple myeloma.Cell death & disease · 2019Article
- SDF1α-induced chemotaxis of JAK2-V617F-positive cells is dependent on Bruton tyrosine kinase and its downstream targets PI3K/AKT, PLCγ1 and RhoA.Haematologica · 2019Article
- BTK induces CAM-DR through regulation of CXCR4 degradation in multiple myeloma.American journal of translational research · 2019Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Multiple Myeloma (MM) is a haematologic malignancy characterized by the accumulation of clonal plasma cells in the bone marrow. Over the last 10-15 y the introduction of the proteasome-inhibitor bortezomib has improved MM prognosis, however relapse due to bortezomib-resistance is inevitable and the disease, at present, remains incurable. To model bortezomib-resistant MM we generated bortezomib-resistant MM cell lines (n = 4 ) and utilised primary malignant plasma cells from patients relapsing after bortezomib treatment (n = 6 ). We identified enhanced Bruton's tyrosine kinase (BTK) activity in bortezomib-resistant MM cells and found that inhibition of BTK, either pharmacologically with ibrutinib (0.5 μM) or via lenti-viral miRNA-targeted BTK interference, re-sensitized previously bortezomib-resistant MM cells to further bortezomib therapy at a physiologically relevant concentration (5 nM). Further analysis of pro-survival signaling revealed a role for the NF-κB p65 subunit in MM bortezomib-resistance, thus a combination of BTK and NF-κB p65 inhibition, either pharmacologically or via further lenti-viral miRNA NF-κB p65 interference, also restored sensitivity to bortezomib, significantly reducing cell viability (37.5 ± 6 .9 %, ANOVA P ≤ 0 .001). Accordingly, we propose the clinical evaluation of a bortezomib/ibrutinib combination therapy, including in patients resistant to single-agent bortezomib.
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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.