ArticleThe Prostate2019
TGF-β receptor I inhibitor enhances response to enzalutamide in a pre-clinical model of advanced prostate cancer.
Article in The Prostate, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 63 citations in OpenAlex.
- Transcriptional profiling identifies an androgen receptor activity-low, stemness program associated with enzalutamide resistance.Proceedings of the National Academy of Sciences of the United States of America · 2020Trial
- Platelet-Prostate cancer crosstalk driving disparities and therapeutic vulnerabilities.Discover oncology · 2026Review
- Tumor microenvironment-driven drug resistance in urologic cancers: mechanisms and therapeutic targets.Genes & genomics · 2026Review
- Identification of a Prognostic ceRNA Network Regulating TMBIM6 in Prostate Adenocarcinoma via Integrated Bioinformatic Analysis.International journal of molecular sciences · 2025Article
- Insights into the relevance of targeting fibroblasts to control cancer.Cell reports. Medicine · 2025Review
- FMNL2/SRC-mediated androgen receptor translocation into the nucleus promotes enzalutamide resistance of prostate cancer.iScience · 2025Article
- An update on cancer stem cell survival pathways involved in chemoresistance in triple-negative breast cancer.Future oncology (London, England) · 2025Review
- Advances in research regarding epithelial-mesenchymal transition and prostate cancer.Frontiers in cell and developmental biology · 2025Review
- Deciphering the Tumor Microenvironment in Prostate Cancer: A Focus on the Stromal Component.Cancers · 2024Review
- Key genes and molecular mechanisms related to Paclitaxel Resistance.Cancer cell international · 2024Review
- Impact of cell plasticity on prostate tumor heterogeneity and therapeutic response.American journal of clinical and experimental urology · 2024Review
- Role of actin-binding proteins in prostate cancer.Frontiers in cell and developmental biology · 2024Review
- A review of biological targets and therapeutic approaches in the management of triple-negative breast cancer.Journal of advanced research · 2023Review
- Androgen receptor inhibition suppresses anti-tumor neutrophil response against bone metastatic prostate cancer via regulation of TβRI expression.Cancer letters · 2023Article
- The screening, identification, design and clinical application of tumor-specific neoantigens for TCR-T cells.Molecular cancer · 2023Review
- GATA2 co-opts TGFβ1/SMAD4 oncogenic signaling and inherited variants at 6q22 to modulate prostate cancer progression.Journal of experimental & clinical cancer research : CR · 2023Article
- Epithelial-Mesenchymal Transition Mechanisms in Chronic Airway Diseases: A Common Process to Target?International journal of molecular sciences · 2023Review
- Anoikis in phenotypic reprogramming of the prostate tumor microenvironment.Frontiers in endocrinology · 2023Review
- The effects of epithelial-mesenchymal transitions in COPD induced by cigarette smoke: an update.Respiratory research · 2022Review
- A Novel Enolase-1 Antibody Targets Multiple Interacting Players in the Tumor Microenvironment of Advanced Prostate Cancer.Molecular cancer therapeutics · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundProstate cancer progression is navigated by the androgen receptor (AR) and transforming-growth factor-β (TGF-β) signaling. We previously demonstrated that aberrant TGF-β signaling accelerates prostate tumor progression in a transgenic mouse model of prostate cancer via effects on epithelial-mesenchymal transition (EMT), driving castration-resistant prostate cancer (CRPC).
methodsThis study examined the antitumor effect of the combination of TGF-β receptor I (TβRI) inhibitor, galunisertib, and FDA-approved antiandrogen enzalutamide, in our pre-clinical model. Age-matched genotypically characterized DNTGFβRII male mice were treated with either galunisertib and enzalutamide, in combination or as single agents in three "mini"-trials and the effects on tumor growth, phenotypic EMT, and actin cytoskeleton were evaluated.
resultsGalunisertib in combination with enzalutamide significantly suppressed prostate tumor growth, by increasing apoptosis and decreasing cell proliferation of tumor cell populations compared to the inhibitor as a monotherapy (P < 0.05). The combination treatment dramatically reduced cofilin levels, actin cytoskeleton regulator, compared to single agents. Treatment with galunisertib targeted nuclear Smad4 protein (intracellular TGF-β effector), but had no effect on nuclear AR. Consequential to TGF-β inhibition there was an EMT reversion to mesenchymal-epithelial transition (MET) and re-differentiation of prostate tumors. Elevated intratumoral TGF-β1 ligand, in response to galunisertib, was blocked by enzalutamide.
conclusionOur results provide novel insights into the therapeutic value of targeting TGF-β signaling to overcome resistance to enzalutamide in prostate cancer by phenotypic reprogramming of EMT towards tumor re-differentiation and cytoskeleton remodeling. This translational work is significant in sequencing TGF-β blockade and antiandrogens to optimize therapeutic response in CRPC.
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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.