Prostate cancer (PCa) remains a leading cause of cancer-related mortality globally, with late-stage diagnoses contributing to poor outcomes. Current screening methods, such as prostate-specific antigen (PSA) testing, suffer from low specificity, leading to unnecessary biopsies and overtreatment. This review underscores the transformative potential of exosomes—nanoscale extracellular vesicles—as non-invasive biomarkers and therapeutic tools in PCa, addressing unmet clinical needs in early detection, treatment resistance, and prognosis.
Introduction
PCa's insidious onset and progression to castration-resistant prostate cancer (CRPC) highlight the urgency for precise biomarkers and targeted therapies. Exosomes, secreted by all cells, carry tumor-derived DNA, RNA, and proteins, offering a "liquid biopsy" platform. Their stability in bodily fluids, minimal invasiveness, and real-time disease monitoring capabilities position them as superior alternatives to traditional methods.
Structure and Function of Exosomes
Exosomes (30–150 nm) are lipid-bilayer vesicles enriched with proteins, miRNAs, lncRNAs, and circRNAs. Their cargo reflects the physiological state of parent cells, enabling intercellular communication. Tumor-derived exosomes influence metastasis, drug resistance, and immune evasion by remodeling the tumor microenvironment (TME). For instance, exosomal miR-95 from tumor-associated macrophages promotes epithelial-mesenchymal transition (EMT) in PCa via JunB targeting.
Exosomes in Prostate Cancer
Diagnosis: Overcoming PSA Limitations
Exosomal biomarkers enhance diagnostic specificity and sensitivity:
miRNAs: miR-19b-3p and miR-101-3p distinguish metastatic from non-metastatic PCa. miR-20b-5p in prostatic fluid and miR-375 in plasma correlate with tumor aggressiveness.
Proteins: Overexpression of prostate-specific membrane antigen (PSMA) and caveolin-1 in exosomes differentiates PCa from benign prostatic hyperplasia (BPH).
lncRNAs: Urinary lncRNAs outperform PSA in detecting clinically significant PCa.
Combining multiple biomarkers (e.g., miR-141-3p and miR-125a-5p) improves accuracy, reducing unnecessary biopsies.
Treatment: Targeting Resistance and Delivery
Exosomes play dual roles—mediating drug resistance and serving as therapeutic vehicles:
Resistance Mechanisms: Cancer-associated fibroblast (CAF)-derived exosomal miR-423-5p suppresses GREM2 via TGF-β, fostering taxane resistance. Similarly, lncRNA ROR activates β-catenin/HIF1α loops, reducing docetaxel (DTX) efficacy.
Drug Delivery: Exosomes efficiently transport chemotherapeutics (e.g., paclitaxel) and gene regulators (e.g., tumor-suppressor miR-let-7c) to PCa cells. Engineered exosomes loaded with TGF-β inhibitors or TLR7/8 agonists show promise in preclinical models.
Prognosis: Predicting Metastasis and Survival
Exosomal cargo predicts metastatic potential and survival:
Metastasis: miR-500a-3p and PGAM1 in exosomes drive angiogenesis and osteoblastic bone metastasis. HOXD-AS1 lncRNA promotes metastasis via miR-361-5p/FOXM1 signaling.
Survival: Low miR-150-5p and high miR-1290 levels correlate with poor overall survival in CRPC. Exosomal miR-375 and miR-1275 predict bone metastasis and therapeutic response.
Challenges and Future Directions
Despite their promise, exosome applications face hurdles:
Technical Barriers: Current isolation methods (e.g., ultracentrifugation) are costly and inefficient. Standardized protocols for purity and dosage are lacking.
Clinical Translation: Most studies are preclinical, with small sample sizes. Large-scale trials are needed to validate biomarkers like circTFDP2 and ZNF667-AS1.
Innovative Strategies: Radiolabeled exosomes for imaging and engineered vesicles for targeted delivery represent emerging frontiers.
Conclusion
Exosomes revolutionize PCa management by enabling early detection, personalized therapy, and dynamic prognosis monitoring. Their ability to encapsulate tumor-specific molecules offers unparalleled insights into PCa biology. However, overcoming technical limitations and advancing clinical validation are critical to harnessing their full potential. As research progresses, exosome-based liquid biopsies may redefine standards of care, reducing morbidity and mortality in PCa patients.
Full text
https://www.xiahepublishing.com/2835-3315/CSP-2024-00029
The study was recently published in the Cancer Screening and Prevention .
Cancer Screening and Prevention (CSP) publishes high-quality research and review articles related to cancer screening and prevention. It aims to provide a platform for studies that develop innovative and creative strategies and precise models for screening, early detection, and prevention of various cancers. Studies on the integration of precision cancer prevention multiomics where cancer screening, early detection and prevention regimens can precisely reflect the risk of cancer from dissected genomic and environmental parameters are particularly welcome.
