ArticleJournal for immunotherapy of cancer2023
Fulvestrant increases the susceptibility of enzalutamide-resistant prostate cancer cells to NK-mediated lysis.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 7 citations in OpenAlex.
- Molecular regulation of estrogen receptors and recent advances on ERα36 splice variant in prostate cancer.Journal of the Endocrine Society · 2026Article
- PARP inhibitors restore NK cell function via secretory crosstalk with tumor cells in prostate cancer.The Journal of clinical investigation · 2026Article
- The Role of Estrogen Signaling Pathway and Targeted Therapy Exploration in Urological Tumors.International journal of biological sciences · 2026Review
- The ATR inhibitor tuvusertib (M1774) sensitizes prostate carcinoma to natural killer cell-mediated cytotoxicity, which is further augmented by the IL-15 receptor superagonist N-803.Cancer immunology, immunotherapy : CII · 2025Article
- PDGFC facilitates enzalutamide resistance in prostate cancer through activation of the Rap1-MAPK pathway.Journal of cancer research and clinical oncology · 2025Article
- Mechanisms and Therapeutic Strategies to Overcome Enzalutamide Resistance in Advanced Prostate Cancer.Serican journal of medicine · 2025Article
- Role of Tumor Microenvironment in Prostate Cancer Immunometabolism.Biomolecules · 2025Review
- Tracing the Evolution of Sex Hormones and Receptor-Mediated Immune Microenvironmental Differences in Prostate and Bladder Cancers: From Embryonic Development to Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- The Oncopromoting Gene RBM6 Inhibits Prostate Tumour Cell Migration During Epithelial-to-Mesenchymal Transition.Journal of cellular and molecular medicine · 2025Article
- Sex bias in tumor immunity: insights from immune cells.Theranostics · 2025Review
- Dynamic interplay of nuclear receptors in tumor cell plasticity and drug resistance: Shifting gears in malignant transformations and applications in cancer therapeutics.Cancer metastasis reviews · 2024Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundEnzalutamide, a next-generation antiandrogen agent, is approved for the treatment of metastatic castration-resistant prostate cancer (CRPC). While enzalutamide has been shown to improve time to progression and extend overall survival in men with CRPC, the majority of patients ultimately develop resistance to treatment. Immunotherapy approaches have shown limited clinical benefit in this patient population; understanding resistance mechanisms could help develop novel and more effective treatments for CRPC. One of the mechanisms involved in tumor resistance to various therapeutics is tumor phenotypic plasticity, whereby carcinoma cells acquire mesenchymal features with or without the loss of classical epithelial characteristics. This work investigated a potential link between enzalutamide resistance, tumor phenotypic plasticity, and resistance to immune-mediated lysis in prostate cancer.
methodsModels of prostate cancer resistant to enzalutamide were established by long-term exposure of human prostate cancer cell lines to the drug in culture. Tumor cells were evaluated for phenotypic features in vitro and in vivo, as well as for sensitivity to immune effector cell-mediated cytotoxicity.
resultsResistance to enzalutamide was associated with gain of mesenchymal tumor features, upregulation of estrogen receptor expression, and significantly reduced tumor susceptibility to natural killer (NK)-mediated lysis, an effect that was associated with decreased tumor/NK cell conjugate formation with enzalutamide-resistant cells. Fulvestrant, a selective estrogen receptor degrader, restored the formation of target/NK cell conjugates and increased susceptibility to NK cell lysis in vitro. In vivo, fulvestrant demonstrated antitumor activity against enzalutamide-resistant cells, an effect that was associated with activation of NK cells.
conclusionNK cells are emerging as a promising therapeutic approach in prostate cancer. Modifying tumor plasticity via blockade of estrogen receptor with fulvestrant may offer an opportunity for immune intervention via NK cell-based approaches in enzalutamide-resistant CRPC.
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