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Review Open access Jul 2026

Canonical Wnt signaling in the regulation of prostate cancer stem cells: a key driver of castration-resistant prostate cancer and a therapeutic opportunity

Prostate cancer (PCa) is the second leading cause of cancer-related death among men worldwide. Although androgen deprivation therapy (ADT) effectively suppresses tumor growth, most patients eventually progress to castration-resistant prostate cancer (CRPC) and develop metastatic disease. The self-renewal, lineage plasticity, epithelial–mesenchymal transition (EMT), and bone metastatic capacity of prostate cancer stem cells (PCSCs) are central drivers of CRPC progression, therapeutic resistance, and metastasis, and the aberrant activation of the canonical Wnt signaling pathway plays a key regulatory role in this process. This review systematically discusses PCSC markers and their applications in clinical diagnosis, elucidates the molecular mechanisms by which aberrant activation of the canonical Wnt signaling pathway, induced by the synergistic effects of genetic mutations, non-coding RNA (ncRNA) dysregulation, epigenetic dysregulation, tumor microenvironment (TME) alterations, and synergistic crosstalk with androgen receptor (AR) signaling, PI3K/AKT/mTOR signaling, Hippo–YAP/TAZ signaling, and metabolic reprogramming, enhances the stemness of PCSCs and promotes their EMT and bone metastasis. We also summarize current research on therapeutic agents targeting the canonical Wnt signaling pathway to suppress PCSCs, along with major challenges in clinical translation and potential strategies to overcome them. Collectively, we propose that targeting this pathway to inhibit PCSCs represents a highly promising strategy for controlling CRPC progression, overcoming therapeutic resistance, and ultimately improving patient outcomes.

Hao-Ze Li, Hong-Tao Xu, Yifan Hou et al. · 0 citations
Open access Aug 2026

Safety, accuracy, empathic communication, information quality, and readability of five large language model interfaces answering public questions about interstitial cystitis/bladder pain syndrome

Background/objectives Patients increasingly use large language model (LLM) interfaces for health information, but their safety and quality for public questions about interstitial cystitis/bladder pain syndrome (IC/BPS) remain uncertain. This study evaluated the safety, accuracy, empathic communication, information quality, reliability, and readability of five publicly accessible LLM interfaces. Methods In this CHART-guided cross-sectional comparative study, 58 public-facing IC/BPS questions were submitted once, in English, to ChatGPT, Gemini, Microsoft Copilot, DeepSeek, and Doubao using a standardized single-turn, zero-shot protocol. Three blinded senior urologists independently assessed safety, accuracy, empathic communication, DISCERN, EQIP, JAMA benchmark criteria, and Global Quality Score. Six readability indices were calculated. Results Inter-rater agreement was significant for all manually assessed metrics. Fleiss’ kappa for safety was 0.822, and ICC(2,1) values for other rater-assessed metrics ranged from 0.761 to 0.848. Unsafe responses occurred in all interfaces, ranging from 5.2% for ChatGPT to 8.6% for DeepSeek and Doubao, without a significant between-interface difference (Cochran Q = 1.000, p = 0.910). Accuracy and empathic communication differed significantly across interfaces (both p < 0.001). ChatGPT had the highest median accuracy score, whereas DeepSeek had the highest empathic communication score. Information-quality and reliability scores also differed significantly (all p < 0.001); ChatGPT achieved higher DISCERN, EQIP, and GQS scores, while Gemini achieved higher JAMA scores. Readability differed significantly across interfaces, but none met predefined patient-facing readability benchmarks. Conclusion Publicly accessible LLM interfaces showed domain-specific differences when answering IC/BPS-related public questions. Unsafe responses were uncommon but present in all interfaces, and no interface consistently outperformed the others. LLM interfaces may support general IC/BPS education and question preparation but should not replace clinician-led evaluation or individualized medical advice.

Jiang-Tao Zhu, Zhen-Hua Zhao, Song Li et al. · 0 citations

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