Prostate Cancer-Associated Fibroblasts: A Review on CAF Functions, Heterogeneity, Resistance Mechanisms, and Future...

Area of Science:

• Oncology
• Cancer Biology
• Tumor Microenvironment Research

Background:

• Cancer-associated fibroblasts (CAFs) are crucial components of the tumor microenvironment (TME) in prostate cancer (PCa).
• CAFs exhibit significant functional heterogeneity due to diverse origins and plasticity, complicating their study and therapeutic targeting.
• CAFs influence PCa progression by promoting extracellular matrix remodeling, angiogenesis, metabolic reprogramming, and immune evasion, contributing to therapy resistance.

Purpose of the Study:

• To review current understanding of CAF heterogeneity and their role in PCa therapy resistance.
• To highlight the potential of organ-on-a-chip (OOC) models for investigating TME interactions and evaluating CAF-targeted strategies.
• To guide the development of novel therapies that disrupt the PCa TME by targeting CAFs.

Main Methods:

• Literature review of CAF biology, heterogeneity, and function in prostate cancer.
• Analysis of CAF contributions to resistance against androgen receptor pathway inhibitors, chemotherapy, and radiotherapy.
• Exploration of emerging organ-on-a-chip (OOC) models for studying tumor-stroma interactions and therapeutic strategies.

Main Results:

• Prostate cancer-associated fibroblasts (CAFs) display complex, context-dependent functions that hinder effective therapeutic targeting.
• CAF subpopulations exhibit overlapping biomarker patterns, making specific identification and functional assessment challenging.
• CAFs promote resistance to multiple standard PCa treatments, underscoring their significance as therapeutic targets.

Conclusions:

• Understanding CAF heterogeneity is critical for developing effective prostate cancer therapies.
• Organ-on-a-chip (OOC) models provide a physiologically relevant platform for studying CAF functions and testing novel therapeutic interventions.
• Targeting CAFs holds promise for overcoming treatment resistance in prostate cancer, but requires sophisticated approaches due to their complex roles.