ArticleCancer letters2024
Dual inhibition of the TrkA and JAK2 pathways using entrectinib and pacritinib suppresses the growth and metastasis of HER2-positive and triple-negative breast cancers.
Article in Cancer letters, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Dual inhibitors of CDK2 and TRKA kinases: design, synthesis, antiproliferative activity and molecular modeling of novel pyrazolopyrimidine derivatives.RSC advances · 2026Article
- A Small Natural Molecule Targeting IL-23/IL-17 Axis Exerts Dual Effects on T-Cell Function and Breast Cancer Cell Migration.Medical sciences (Basel, Switzerland) · 2026Article
- Flavonoid-modulated JAK-STAT signaling mitigates malignant transformation and drug resistance in breast tumors: A clinically relevant 3PM-guided innovation.Journal of advanced research · 2026Review
- Decoding triple negative breast cancer bone metastasis: from 3D bioprinted models to clinical translation.Journal of nanobiotechnology · 2026Review
- Hijacking the bone niche: mechanistic insights into bone metastasis in breast cancer.Bone research · 2026Review
- 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
- Recent advances in targeted therapies and immunotherapies for triple-negative breast cancer.Frontiers in oncology · 2026Review
- Trk Signaling Inhibition Reduces cSCC Growth and Invasion in In Vitro and Zebrafish Models and Enhances Photodynamic Therapy Outcome.International journal of molecular sciences · 2025Article
- NIBAN2 Stimulates Glioma Growth by Regulating the JAK2/STAT3/c-Myc Pathway.Cancer medicine · 2025Article
- JAK2 Inhibition Augments the Anti-Proliferation Effects by AKT and MEK Inhibition in Triple-Negative Breast Cancer Cells.International journal of molecular sciences · 2025Article
- Heterogeneous tissue-specific macrophages orchestrate metastatic organotropism of breast cancer: implications for promising therapeutics.Journal of translational medicine · 2025Review
- Napabucasin targets resistant triple negative breast cancer through suppressing STAT3 and mitochondrial function.Cancer chemotherapy and pharmacology · 2025Article
- Immunotherapy resistance in triple-negative breast cancer: Molecular mechanisms, tumor microenvironment, and therapeutic implications.Frontiers in oncology · 2025Review
- 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
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Authors and funding
11 authors.
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Abstract
HER2-positive and triple-negative breast cancers (TNBC) are difficult to treat and associated with poor prognosis. Despite showing initial response, HER2-positive breast cancers often acquire resistance to HER2-targeted therapies, and TNBC lack effective therapies. To overcome these clinical challenges, we evaluated the therapeutic utility of co-targeting TrkA and JAK2/STAT3 pathways in these breast cancer subtypes. Here, we report the novel combination of FDA-approved TrkA inhibitors (Entrectinib or Larotrectinib) and JAK2 inhibitors (Pacritinib or Ruxolitinib) synergistically inhibited in vitro growth of HER2-positive breast cancer cells and TNBC cells. The Entrectinib-Pacritinib combination inhibited the breast cancer stem cell subpopulation, reduced expression of stemness genes, SOX2 and MYC, and induced apoptosis. The Entrectinib-Pacritinib combination suppressed orthotopic growth of HER2-positive Trastuzumab-refractory breast cancer xenografts and basal patient-derived xenograft (PDXs), reduced tumoral SOX2 and MYC, and induced apoptosis in both mouse models. The Entrectinib-Pacritinib combination inhibited overall metastatic burden, and brain and bone metastases of intracardially inoculated TNBC cells without toxicity. Together, our results demonstrate for the first time that co-inhibition of TrkA and JAK2 synergistically suppresses breast cancer growth and metastasis, thereby providing preclinical evidence that supports future clinical evaluations.
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