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Progress in Modelling, Understanding of Cellular Biology of Prostate Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (31 August 2025) | Viewed by 284

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Guest Editor
Department of Urology, University of Kansas Medical Center, Kansas City, MO, USA
Interests: prostate cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Prostate cancer remains a significant public health challenge, with rising incidence rates and substantial mortality among men worldwide. Recent advancements in modeling and understanding the cellular biology of prostate cancer have opened new avenues for targeted therapies and personalized medicine. Traditional approaches to prostate cancer research have evolved, incorporating sophisticated techniques such as three-dimensional tissue cultures, organoids, and computational modeling. These methodologies enhance our understanding of tumor heterogeneity, microenvironment interactions, and the molecular pathways driving disease progression. Furthermore, integrating genomic and proteomic data has illuminated the complex cellular networks involved in prostate cancer, enabling researchers to identify potential biomarkers and therapeutic targets. This Special Issue aims to highlight recent progress in these fields, underscoring the importance of a multidisciplinary approach to unraveling prostate cancer biology's intricacies and improving patient clinical outcomes.

Prof. Dr. Benyi Li
Guest Editor

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Keywords

  • prostate cancer
  • cellular biology
  • targeted therapy

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Published Papers (1 paper)

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Research

19 pages, 7006 KB  
Article
Dynamic Reprogramming of Immune-Related Signaling During Progression to Enzalutamide Resistance in Prostate Cancer
by Pengfei Xu, Huan Qu, Joy C. Yang, Fan Wei, Junwei Zhao, Menghuan Tang, Leyi Wang, Christopher Nip, Henson Li, Allen C. Gao, Kit Lam, Marc Dall'Era, Yuanpei Li and Chengfei Liu
Cancers 2025, 17(19), 3187; https://doi.org/10.3390/cancers17193187 - 30 Sep 2025
Abstract
Background: Treatment with androgen receptor (AR) signaling inhibitors, such as enzalutamide, can induce neural lineage plasticity in prostate cancer, potentially progressing to t-NEPC. However, the molecular mechanisms underlying this enzalutamide-driven plasticity, particularly the contribution of immune signaling pathways, remain poorly understood. Methods: We [...] Read more.
Background: Treatment with androgen receptor (AR) signaling inhibitors, such as enzalutamide, can induce neural lineage plasticity in prostate cancer, potentially progressing to t-NEPC. However, the molecular mechanisms underlying this enzalutamide-driven plasticity, particularly the contribution of immune signaling pathways, remain poorly understood. Methods: We analyzed transcriptomic profiles of patient samples and prostate cancer cell lines to investigate changes in immune signaling pathways. Interferon gamma (IFNγ), interferon alpha (IFNα), and interleukin 6 (IL6)-Janus kinase (JAK)-signal transducer and activator of transcription 3 (STAT3) signaling were assessed in enzalutamide-sensitive and -resistant prostate cancer cells. Functional assays were conducted to examine cell responsiveness to cytokine stimulation and susceptibility to STAT1 inhibition using fludarabine. Results: Immune-related pathways, including IFNγ, IFNα, IL6-JAK-STAT3, and inflammatory responses, were significantly suppressed in NEPC patient samples compared to those with castration-resistant prostate cancer (CRPC). Enzalutamide-resistant and NEPC cells exhibited markedly impaired IFNγ and IL6 signaling. In contrast, early-stage enzalutamide treatment paradoxically enhanced IFNγ and IL6 responsiveness. Transcriptomic profiling revealed coordinated upregulation of E2F target genes and activation of IFNα/IFNγ and JAK/STAT signaling pathways during early treatment. Importantly, these early-stage cells remained highly sensitive to IFNγ and IL6 stimulation and showed increased susceptibility to STAT1 inhibition by fludarabine, a sensitivity that was lost in resistant cells. Conclusions: Early enzalutamide treatment enhances immune responsiveness, while the development of resistance is associated with suppressed immune signaling and increased lineage plasticity. These results suggest a therapeutic window where combining enzalutamide with STAT inhibitors may delay or prevent lineage plasticity and resistance. Full article
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