ArticleOncogene2020
Combined inhibition of JAK2-STAT3 and SMO-GLI1/tGLI1 pathways suppresses breast cancer stem cells, tumor growth, and metastasis.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 48 papers, 1 of them a synthesis that pooled it.
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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
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- Regulation and therapy, the role of JAK2/STAT3 signaling pathway in OA: a systematic review.Cell communication and signaling : CCS · 2023Pooled it
- An open-label, pilot study of veliparib and lapatinib in patients with metastatic, triple-negative breast cancer.Breast cancer research : BCR · 2021Trial
- RET receptor tyrosine kinase promotes breast cancer metastasis to the brain and RET inhibitors pralsetinib and selpercatinib suppress breast cancer brain metastases.Cell death & disease · 2026Article
- PFDN5 synergizes with anti-PD1 therapy to promote triple-negative breast cancer cell death through JAK2/STAT3/c-Myc signaling axis.Journal of translational medicine · 2026Article
- Pharmacological targeting of the JAK-STAT pathway: new concepts and emerging indications.Nature reviews. Drug discovery · 2026Review
- Review
- Convergent systemic therapy for liver metastases: Bridging primary tumor heterogeneity through shared pathways.iLIVER · 2025Review
- Hedgehog inhibitors exert anti-proliferation effects and synergistically interact with trastuzumab in HER2-positive gastric cancer models.Acta oncologica (Stockholm, Sweden) · 2025Article
- Lipocalin-2 promotes NSCLC progression by activating the JAK2/STAT3 signaling pathway.Journal of translational medicine · 2025Article
- Review
- Distribution and clinicopathological characteristics of G-CSF expression in tumor cells and stromal cells in upper tract urothelial carcinoma.Journal of cancer research and clinical oncology · 2024Article
- Targeting STAT3 signaling pathway by curcumin and its analogues for breast cancer: A narrative review.Animal models and experimental medicine · 2024Review
- STAT3: Key targets of growth-promoting receptor positive breast cancer.Cancer cell international · 2024Review
- Biological Evaluations and Computer-Aided Approaches of Janus Kinases 2 and 3 Inhibitors for Cancer Treatment: A Review.Pharmaceutics · 2024Review
- Pharmacokinetics and Bioavailability Study of a Novel Smoothened Inhibitor TPB15 for Treatment of Triple-Negative Breast Cancer in Rats by High Performance Liquid Chromatography-Mass Spectrometry.European journal of drug metabolism and pharmacokinetics · 2024Article
- Piperlongumine: the amazing amide alkaloid from Piper in the treatment of breast cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- FOXA3 regulates cholesterol metabolism to compensate for low uptake during the progression of lung adenocarcinoma.PLoS biology · 2024Article
- Article
- Ruxolitinib induces apoptosis and pyroptosis of anaplastic thyroid cancer via the transcriptional inhibition of DRP1-mediated mitochondrial fission.Cell death & disease · 2024Article
- Unveiling Epigenetic Vulnerabilities in Triple-Negative Breast Cancer through 3D Organoid Drug Screening.Pharmaceuticals (Basel, Switzerland) · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
Triple-negative breast cancer (TNBC) and HER2-positive breast cancer are particularly aggressive and associated with unfavorable prognosis. TNBC lacks effective treatments. HER2-positive tumors have treatment options but often acquire resistance to HER2-targeted therapy after initial response. To address these challenges, we determined whether novel combinations of JAK2-STAT3 and SMO-GLI1/tGLI1 inhibitors synergistically target TNBC and HER2 breast cancer since these two pathways are concurrently activated in both tumor types and enriched in metastatic tumors. Herein, we show that novel combinations of JAK2 inhibitors (ruxolitinib and pacritinib) with SMO inhibitors (vismodegib and sonidegib) synergistically inhibited in vitro growth of TNBC and HER2-positive trastuzumab-resistant BT474-TtzmR cells. Synergy was also observed against breast cancer stem cells. To determine if the combination is efficacious in inhibiting metastasis, we treated mice with intracardially inoculated TNBC cells and found the combination to inhibit lung and liver metastases, and prolong host survival without toxicity. The combination inhibited orthotopic growth, VEGF-A expression, and tumor vasculature of both TNBC and HER2-positive trastuzumab-refractory breast cancer. Lung metastasis of orthotopic BT474-TtzmR xenografts was suppressed by the combination. Together, our results indicated that dual targeting of JAK2 and SMO resulted in synergistic suppression of breast cancer growth and metastasis, thereby supporting future clinical testing.
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