# Cancer-Associated Fibroblasts in Prostate Cancer: Unraveling Mechanisms and Therapeutic Implications

## TL;DR

This review explores how cancer-associated fibroblasts influence prostate cancer progression and resistance to treatment, offering insights into new therapeutic strategies.

## Contribution

The paper provides a comprehensive overview of CAF heterogeneity and mechanisms in prostate cancer, integrating recent single-cell and spatial transcriptomics data.

## Key findings

- CAFs originate from multiple cell types and contribute to tumor progression through crosstalk with other TME components.
- CAFs promote therapy resistance and metastasis by modulating immune evasion, angiogenesis, and metabolic reprogramming.
- Emerging strategies to target CAF-mediated pathways offer potential for stromal reprogramming in prostate cancer treatment.

## Abstract

Prostate cancer (PCa) remains a major cause of cancer-related mortality in men, largely due to therapy resistance and metastatic progression. Increasing evidence highlights the tumor microenvironment (TME), particularly cancer-associated fibroblasts (CAFs), as a critical determinant of disease behavior. CAFs constitute a heterogeneous population originating from fibroblasts, mesenchymal stem cells, endothelial cells, epithelial cells undergoing epithelial–mesenchymal transition (EMT), and adipose tissue. Through dynamic crosstalk with tumor, immune, endothelial, and adipocyte compartments, CAFs orchestrate oncogenic processes including tumor proliferation, invasion, immune evasion, extracellular matrix remodeling, angiogenesis, and metabolic reprogramming. This review comprehensively summarizes the cellular origins, phenotypic and functional heterogeneity, and spatial distribution of CAFs within the prostate TME. We further elucidate the molecular mechanisms by which CAFs regulate PCa progression and therapeutic resistance, and critically evaluate emerging strategies to therapeutically target CAF-mediated signaling, metabolic, and immune pathways. By integrating recent advances from single-cell and spatial transcriptomics (ST), our objective is to provide a holistic framework for understanding CAF biology and to highlight potential avenues for stromal reprogramming as an adjunct to current PCa therapies.