ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
Pharmacologic inhibition of Jak2-Stat5 signaling By Jak2 inhibitor AZD1480 potently suppresses growth of both primary and castrate-resistant prostate cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses that pooled it.
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Who cites it
42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 54 citations in OpenAlex.
- Expression and prognostic role of STAT5a across cancer types.Bioscience reports · 2023Pooled it
- Relevance of humanized three-dimensional tumor tissue models: a descriptive systematic literature review.Cellular and molecular life sciences : CMLS · 2020Pooled it
- JAK-STAT signaling pathway in cancer: from molecular mechanisms to clinical intervention.Molecular cancer · 2026Review
- Non-Canonical TERT Activity Initiates Osteogenesis in Calcific Aortic Valve Disease.Circulation research · 2025Article
- Dorsomorphin Suppresses EMT to Reduce AR-Negative Prostate Cancer Metastasis by Synergistically Antagonizing JAK2/STAT3 and Gli2-Independent Shh Activation.Prostate cancer · 2025Article
- Investigating the Potential Effects of 6PPDQ on Prostate Cancer Through Network Toxicology and Molecular Docking.Toxics · 2024Article
- Stat5 induces androgen receptor (Science advances · 2024Article
- Choosing Kinase Inhibitors for Androgen Deprivation Therapy-Resistant Prostate Cancer.Pharmaceutics · 2022Review
- Novel biomarkers predict prognosis and drug-induced neuroendocrine differentiation in patients with prostate cancer.Frontiers in endocrinology · 2022Article
- Article
- Second-Generation Jak2 Inhibitors for Advanced Prostate Cancer: Are We Ready for Clinical Development?Cancers · 2021Review
- Novel Combinatorial Approaches to Tackle the Immunosuppressive Microenvironment of Prostate Cancer.Cancers · 2021Review
- ENC1 Facilitates Colorectal Carcinoma Tumorigenesis and Metastasis via JAK2/STAT5/AKT Axis-Mediated Epithelial Mesenchymal Transition and Stemness.Frontiers in cell and developmental biology · 2021Article
- Article
- Cytokines, JAK-STAT Signaling and Radiation-Induced DNA Repair in Solid Tumors: Novel Opportunities for Radiation Therapy.The international journal of biochemistry & cell biology · 2020Review
- Involvement of STAT5 in Oncogenesis.Biomedicines · 2020Review
- Prolactin Enhances the Proliferation of Proliferative Endometrial Glandular Cells and Endometrial Cancer Cells.Journal of the Endocrine Society · 2020Article
- Assessment of STAT5 as a potential therapy target in enzalutamide-resistant prostate cancer.PloS one · 2020Article
- Positive STAT5 Protein and Locus Amplification Status Predicts Recurrence after Radical Prostatectomy to Assist Clinical Precision Management of Prostate Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2019Article
- Cellular and Molecular Mechanisms Underlying Prostate Cancer Development: Therapeutic Implications.Medicines (Basel, Switzerland) · 2019Review
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
purposeProgression of prostate cancer to the lethal castrate-resistant stage coincides with loss of responsiveness to androgen deprivation and requires development of novel therapies. We previously provided proof-of-concept that Stat5a/b is a therapeutic target protein for prostate cancer. Here, we show that pharmacologic targeting of Jak2-dependent Stat5a/b signaling by the Jak2 inhibitor AZD1480 blocks castrate-resistant growth of prostate cancer. EXPERIMENTAL
designEfficacy of AZD1480 in disrupting Jak2-Stat5a/b signaling and decreasing prostate cancer cell viability was evaluated in prostate cancer cells. A unique prostate cancer xenograft mouse model (CWR22Pc), which mimics prostate cancer clinical progression in patients, was used to assess in vivo responsiveness of primary and castrate-resistant prostate cancer (CRPC) to AZD1480. Patient-derived clinical prostate cancers, grown ex vivo in organ explant cultures, were tested for responsiveness to AZD1480.
resultsAZD1480 robustly inhibited Stat5a/b phosphorylation, dimerization, nuclear translocation, DNA binding, and transcriptional activity in prostate cancer cells. AZD1480 reduced prostate cancer cell viability sustained by Jak2-Stat5a/b signaling through induction of apoptosis, which was rescued by constitutively active Stat5a/b. In mice, pharmacologic targeting of Stat5a/b by AZD1480 potently blocked growth of primary androgen-dependent as well as recurrent castrate-resistant CWR22Pc xenograft tumors, and prolonged survival of tumor-bearing mice versus vehicle or docetaxel-treated mice. Finally, nine of 12 clinical prostate cancers responded to AZD1480 by extensive apoptotic epithelial cell loss, concurrent with reduced levels of nuclear Stat5a/b.
conclusionsWe report the first evidence for efficacy of pharmacologic targeting of Stat5a/b as a strategy to inhibit castrate-resistant growth of prostate cancer, supporting further clinical development of Stat5a/b inhibitors as therapy for advanced prostate cancer.
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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.