Trial reportThe Journal of clinical investigation2014
Targeting an IKBKE cytokine network impairs triple-negative breast cancer growth.
Trial report in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
97 citing papers in PubMed, 1 synthesis or guideline pooled it, 153 citations in OpenAlex.
- Pooled it
- Janus kinases restrain chronic lymphocytic leukemia cells in patients on ibrutinib: Results of a phase II trial.Cancer medicine · 2021Trial
- Current and future therapies for triple-negative breast cancer.Journal of hematology & oncology · 2026Review
- Programmable nanomicelles rewire myeloid immunity for durable control of primary and metastatic breast cancer.Nature communications · 2026Article
- Ex vivo drug sensitivity testing predicts treatment outcomes in advanced ovarian cancer.NPJ precision oncology · 2026Article
- Microglial TBK1 Signaling Promotes Breast Cancer Brain Metastasis.Cancer research · 2026Article
- Phosphoregulation of interleukin-1 receptor-associated kinase 1 in inflammatory signaling.Frontiers in immunology · 2026Review
- Pathogenic role and therapeutic targets of nuclear factor-κB signaling pathway in cancer (Review).Oncology letters · 2025Review
- Macrophage TBK1 signaling drives the development and outgrowth of breast cancer brain metastasis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Matrix stiffness-induced IKBKE and MAPK8 signaling drives a phenotypic switch from DCIS to invasive breast cancer.Cell communication and signaling : CCS · 2025Article
- Atypical inflammatory kinase IKBKE phosphorylates and inactivates FoxA1 to promote liver tumorigenesis.Science advances · 2024Article
- IL-1β mediates the induction of immune checkpoint regulators IDO1 and PD-L1 in lung adenocarcinoma cells.Cell communication and signaling : CCS · 2023Article
- CCL5 might be a prognostic biomarker and associated with immuno-therapeutic efficacy in cancers: A pan-cancer analysis.Heliyon · 2023Article
- DAB2IP Is a Bifunctional Tumor Suppressor That Regulates Wild-Type RAS and Inflammatory Cascades in KRAS Mutant Colon Cancer.Cancer research · 2023Article
- The NF-κB Transcriptional Network Is a High-Dose Vitamin C-Targetable Vulnerability in Breast Cancer.Biomedicines · 2023Review
- The role of Th-17 cells and IL-17 in the metastatic spread of breast cancer: As a means of prognosis and therapeutic target.Frontiers in immunology · 2023Review
- Optimized dose selective HDAC inhibitor tucidinostat overcomes anti-PD-L1 antibody resistance in experimental solid tumors.BMC medicine · 2022Article
- The NF-κB Pharmacopeia: Novel Strategies to Subdue an Intractable Target.Biomedicines · 2022Review
- IKBKE phosphorylates and stabilizes Snail to promote breast cancer invasion and metastasis.Cell death and differentiation · 2022Article
- Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 3 institutions in 1 country.
Funding
Abstract
Triple-negative breast cancers (TNBCs) are a heterogeneous set of cancers that are defined by the absence of hormone receptor expression and HER2 amplification. Here, we found that inducible IκB kinase-related (IKK-related) kinase IKBKE expression and JAK/STAT pathway activation compose a cytokine signaling network in the immune-activated subset of TNBC. We found that treatment of cultured IKBKE-driven breast cancer cells with CYT387, a potent inhibitor of TBK1/IKBKE and JAK signaling, impairs proliferation, while inhibition of JAK alone does not. CYT387 treatment inhibited activation of both NF-κB and STAT and disrupted expression of the protumorigenic cytokines CCL5 and IL-6 in these IKBKE-driven breast cancer cells. Moreover, in 3D culture models, the addition of CCL5 and IL-6 to the media not only promoted tumor spheroid dispersal but also stimulated proliferation and migration of endothelial cells. Interruption of cytokine signaling by CYT387 in vivo impaired the growth of an IKBKE-driven TNBC cell line and patient-derived xenografts (PDXs). A combination of CYT387 therapy with a MEK inhibitor was particularly effective, abrogating tumor growth and angiogenesis in an aggressive PDX model of TNBC. Together, these findings reveal that IKBKE-associated cytokine signaling promotes tumorigenicity of immune-driven TNBC and identify a potential therapeutic strategy using clinically available compounds.
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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.