ArticleCancer research2015
Bruton tyrosine kinase is a therapeutic target in stem-like cells from multiple myeloma.
Article in Cancer research, 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 47 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
47 citing papers in PubMed, 76 citations in OpenAlex.
- A phase 2 study of ibrutinib in combination with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma.European journal of haematology · 2020Trial
- Ibrutinib alone or with dexamethasone for relapsed or relapsed and refractory multiple myeloma: phase 2 trial results.British journal of haematology · 2018Trial
- Ibrutinib in Combination with Lenalidomide Revlimid/Dexamethasone in Relapsed/Refractory Multiple Myeloma (AFT-15).Cancers · 2025Article
- From development to clinical success: the journey of established and next-generation BTK inhibitors.Investigational new drugs · 2025Review
- Inhibition of proteolytic and ATPase activities of the proteasome by the BTK inhibitor CGI-1746.iScience · 2024Article
- Bruton Tyrosine Kinase Inhibition Decreases Inflammation and Differentially Impacts Phagocytosis and Cellular Metabolism in Mouse- and Human-derived Myeloid Cells.ImmunoHorizons · 2024Article
- Pathways to therapy resistance: The sheltering effect of the bone marrow microenvironment to multiple myeloma cells.Heliyon · 2024Review
- Article
- Past, Present, and a Glance into the Future of Multiple Myeloma Treatment.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Molecular and immunological mechanisms of clonal evolution in multiple myeloma.Frontiers in immunology · 2023Review
- Differential Diagnosis and Therapeutic Advances in Multiple Myeloma: A Review Article.Blood and lymphatic cancer : targets and therapy · 2023Review
- BTK inhibitors in the treatment of hematological malignancies and inflammatory diseases: mechanisms and clinical studies.Journal of hematology & oncology · 2022Review
- In silico bioinformatics analysis for identification of differentially expressed genes and therapeutic drug molecules in Glucocorticoid-resistant Multiple myeloma.Medical oncology (Northwood, London, England) · 2022Article
- ALCAM regulates multiple myeloma chemoresistant side population.Cell death & disease · 2022Article
- REC8 enhances stemness and promotes metastasis of colorectal cancer through BTK/Akt/β-catenin signaling pathway.Translational oncology · 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
- Combined Treatment with Acalabrutinib and Rapamycin Inhibits Glioma Stem Cells and Promotes Vascular Normalization by Downregulating BTK/mTOR/VEGF Signaling.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Bruton's tyrosine kinase (BTK) mediates resistance to EGFR inhibition in non-small-cell lung carcinoma.Oncogenesis · 2021Article
- Review
- Bruton's Tyrosine Kinase Targeting in Multiple Myeloma.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Ibrutinib (Imbruvica), a small-drug inhibitor of Bruton tyrosine kinase (BTK), is currently undergoing clinical testing in patients with multiple myeloma, yet important questions on the role of BTK in myeloma biology and treatment are outstanding. Using flow-sorted side population cells from human myeloma cell lines and multiple myeloma primary samples as surrogate for the elusive multiple myeloma stem cell, we found that elevated expression of BTK in myeloma cells leads to AKT/WNT/β-catenin-dependent upregulation of key stemness genes (OCT4, SOX2, NANOG, and MYC) and enhanced self-renewal. Enforced transgenic expression of BTK in myeloma cells increased features of cancer stemness, including clonogenicity and resistance to widely used myeloma drugs, whereas inducible knockdown of BTK abolished them. Furthermore, overexpression of BTK in myeloma cells promoted tumor growth in laboratory mice and rendered side population-derived tumors that contained high levels of BTK more sensitive to the selective, second-generation BTK inhibitor, CGI1746, than side population-derived tumors that harbored low levels of BTK. Taken together, these findings implicate BTK as a positive regulator of myeloma stemness and provide additional support for the clinical testing of BTK-targeted therapies in patients with 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.