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Mechanistic Insights and Therapeutic Advances in the Prostate Tumor Microenvironment

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".

Deadline for manuscript submissions: closed (28 February 2026) | Viewed by 1810

Special Issue Editor


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Guest Editor
Department of Biochemistry and Molecular Biology, Louisiana State University Health Shreveport, Shreveport, LA 71103, USA
Interests: molecular biology; tumor microenvironment; prostate cancer

Special Issue Information

Dear Colleagues,

Prostate cancer (PCa) remains a leading cause of cancer-related death among men and is characterized by complex interactions between tumor cells and their surrounding microenvironment. Composed of fibroblasts, immune cells, endothelial cells, pericytes, and neural elements, the tumor microenvironment (TME) is critical in disease progression, therapeutic resistance, and metastasis. Cancer-associated fibroblasts (CAFs) promote tumor growth, invasion, and immune suppression through the dynamic remodeling of the extracellular matrix and secretion of growth factors. Tumor-associated macrophages (TAMs) and other immune cells contribute to an immunosuppressive milieu, enabling immune evasion and resistance to therapy. In addition, metabolic stressors such as hypoxia and acidosis shape cellular behavior in the TME, inducing treatment resistance and tumor aggressiveness. Interactions with neural components, including sympathetic and parasympathetic nerves, have additionally been implicated in tumor progression and metastatic spread.

We seek original research and reviews that study in vitro, ex vivo, or in vivo TME models, utilizing novel methods and asking thought-provoking questions in examining the role of the TME and its potential as a therapeutic target in prostate cancer.

This Special Issue aims to highlight recent advances in understanding the cellular and molecular mechanisms by which the prostate TME supports cancer development, progression, and therapy resistance.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

  • Cellular and molecular components of the prostate tumor microenvironment;
  • Mechanisms of immune evasion and immunosuppression in the prostate TME;
  • The role of cancer-associated fibroblasts (CAFs) in tumor progression and therapy resistance;
  • Metabolic reprogramming and adaptation within the TME;
  • Crosstalk between tumor cells and the stromal or neural microenvironment;
  • Hypoxia, acidosis, and other microenvironmental stressors shaping tumor behavior;
  • Lineage plasticity promoted by the TME;
  • The influence of the TME on metastatic tropism and organ-specific colonization;
  • TME contributions to racial and molecular disparities in prostate cancer;
  • Targeting the TME with immunotherapies, stromal modulators, or metabolic interventions;
  • The use of novel 3D organoids, ex vivo cultures, and in vivo models to study the prostate TME.

We look forward to receiving your contributions.

Dr. Omar E. Franco
Guest Editor

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Keywords

  • prostate stromal cells
  • tumor microenvironment
  • stromal–epithelial interactions
  • extracellular matrix
  • tumor immune evasion
  • metabolic reprogramming
  • hypoxia
  • single-cell data analysis
  • in vitro/in vivo model systems
  • carcinoma-associated fibroblasts (CAFs)

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Published Papers (1 paper)

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Review

37 pages, 2896 KB  
Review
Targeting Cancer-Associated Fibroblasts in Prostate Cancer: Recent Advances and Therapeutic Opportunities
by Peng Chen, Junhao Chen, Peiqin Zhan, Xinni Ye, Li Zhao, Zhongsong Zhang, Jieming Zuo, Hongjin Shi, Xiangyun Li, Songhong Wu, Yuanzhi Fu, Haifeng Wang and Shi Fu
Cancers 2026, 18(1), 151; https://doi.org/10.3390/cancers18010151 - 31 Dec 2025
Cited by 3 | Viewed by 1537
Abstract
Advanced prostate cancer, particularly castration-resistant disease, remains challenging to treat due to intratumoral heterogeneity, immune exclusion, and a suppressive tumor microenvironment. Within this ecosystem, cancer-associated fibroblasts shape tumor–stroma communication, but their marked heterogeneity and plasticity complicate classification and make indiscriminate fibroblast depletion potentially [...] Read more.
Advanced prostate cancer, particularly castration-resistant disease, remains challenging to treat due to intratumoral heterogeneity, immune exclusion, and a suppressive tumor microenvironment. Within this ecosystem, cancer-associated fibroblasts shape tumor–stroma communication, but their marked heterogeneity and plasticity complicate classification and make indiscriminate fibroblast depletion potentially ineffective or even harmful. This review summarizes recent progress in fibroblast origins, functional subtypes, and fibroblast-driven mechanisms that promote tumor progression and therapy resistance, as well as emerging therapeutic opportunities in prostate cancer. We conducted a structured literature search of PubMed, ScienceDirect, and major publisher platforms (including Nature and SpringerLink) from database inception to 15 February 2025, supplemented by targeted manual screening of reference lists. Evidence from single-cell/spatial-omics and mechanistic studies indicates that prostate tumors contain multiple fibroblast programs that occupy distinct niches yet can interconvert. Across these studies, it was found that these fibroblasts contribute to immune suppression, extracellular matrix remodeling and stromal barrier formation, angiogenesis, and metabolic support, collectively limiting drug penetration and reinforcing immune evasion; therapeutic pressure can further rewire fibroblast states and resistance-associated signaling. Overall, the literature supports a shift toward function- and subtype-directed intervention rather than “one-size-fits-all” targeting, with promising directions including precision targeting and reversible reprogramming, rational combination strategies, and localized delivery approaches that reduce stromal barriers while preserving tissue homeostasis in high-risk and treatment-refractory prostate cancer. Full article
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