ArticleMolecular cancer therapeutics2022
Bioengineered BERA-Wnt5a siRNA Targeting Wnt5a/FZD2 Signaling Suppresses Advanced Prostate Cancer Tumor Growth and Enhances Enzalutamide Treatment.
Article in Molecular cancer therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Efficacy of Bioengineered PD-L1 siRNA for Immunotherapy Against Non-Small Cell Lung Cancer Cells.Non-coding RNA · 2026Article
- WNT signaling in cancer: molecular mechanisms and potential therapies.Molecular biomedicine · 2025Review
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Unveiling the Therapeutic Potential: A Peptide Drug Conjugate's Influence on Transcription and Translation in Ocular Fibrosis Modulation.ACS omega · 2025Article
- Wnt/CaOncology letters · 2025Review
- SOX2 utilizes FOXA1 as a heteromeric transcriptional partner to drive proliferation in therapy-resistant prostate cancer.bioRxiv : the preprint server for biology · 2025Article
- Recent advances in understanding the role of Wnt5a in prostate cancer and bone metastasis.Discover oncology · 2025Review
- In Vivo Fermentation Production of RNA Interference Agents.Methods in molecular biology (Clifton, N.J.) · 2025Article
- The role of the LncRNA XIST/miR-15a-5p/MN1 signaling axis in gender disparities in bladder cancer prognosis.Frontiers in immunology · 2025Article
- Pan-cancer profiling of FZD2 as a prognostic biomarker: integrative multi-omics analysis with experimental validation and functional characterization in gastric cancer.Frontiers in pharmacology · 2025Article
- Comparison of Three Computational Tools for the Prediction of RNA Tertiary Structures.Non-coding RNA · 2024Article
- Current uses and resistance mechanisms of enzalutamide in prostate cancer treatment.Expert review of anticancer therapy · 2024Review
- Frizzled receptors (FZDs) in Wnt signaling: potential therapeutic targets for human cancers.Acta pharmacologica Sinica · 2024Review
- Inhibition of iRhom1 by CD44-targeting nanocarrier for improved cancer immunochemotherapy.Nature communications · 2024Article
- Efflux ABC transporters in drug disposition and their posttranscriptional gene regulation by microRNAs.Frontiers in pharmacology · 2024Review
- Altered binding affinity of SIX1-Q177R correlates with enhanced WNT5A and WNT pathway effector expression in Wilms tumor.Disease models & mechanisms · 2023Article
- WNT5a Signaling through ROR2 Activates the Hippo Pathway to Suppress YAP1 Activity and Tumor Growth.Cancer research · 2023Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
The next-generation antiandrogen drugs such as enzalutamide and abiraterone extend survival times and improve quality of life in patients with advanced prostate cancer. However, resistance to both drugs occurs frequently through mechanisms that are incompletely understood. Wnt signaling, particularly through Wnt5a, plays vital roles in promoting prostate cancer progression and induction of resistance to enzalutamide and abiraterone. Development of novel strategies targeting Wnt5a to overcome resistance is an urgent need. In this study, we demonstrated that Wnt5a/FZD2-mediated noncanonical Wnt pathway is overexpressed in enzalutamide-resistant prostate cancer. In patient databases, both the levels of Wnt5a and FZD2 expression are upregulated upon the development of enzalutamide resistance and correlate with higher Gleason score, biochemical recurrence, and metastatic status, and with shortened disease-free survival duration. Blocking Wnt5a/FZD2 signal transduction not only diminished the activation of noncanonical Wnt signaling pathway, but also suppressed the constitutively activated androgen receptor (AR) and AR variants. Furthermore, we developed a novel bioengineered BERA-Wnt5a siRNA construct and demonstrated that inhibition of Wnt5a expression by the BERA-Wnt5a siRNA significantly suppressed tumor growth and enhanced enzalutamide treatment in vivo. These results indicate that Wnt5a/FZD2 signal pathway plays a critical role in promoting enzalutamide resistance, and targeting this pathway by BERA-Wnt5a siRNA can be developed as a potential therapy to treat advanced prostate cancer.
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Registered trials
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