Therapeutic ambitions, diagnostic advantages, and functional divergence of pancreatic cancer-derived exosomes towards optimized disease management

胰腺癌来源外泌体的治疗目标、诊断优势和功能差异,旨在优化疾病管理

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of pancreatic cancer (PC). The inefficient early detection and screening methods make PDAC the fourth deadliest cancer worldwide. The adjuvant and neoadjuvant therapies can manage the disease, but often with very low efficacy, resulting in a low 5-year survival rate of just 12%. Site-specific drug targeting and more precise early detection could be the way forward. Biological vehicles, like exosomes, a type of extracellular vesicle, play a crucial role in the development and metastasis of various types of cancer, including PC. By nature, exosomes are nano-sized vesicles secreted by most cells, including cancer cells. They carry biologically active molecules that facilitate cell-cell communication and signaling and are specific for each type of cancer, including PDACs. These PC-secreted exosomes have a unique molecular signature that is being investigated for PC diagnosis. Additionally, these vesicles could be engineered biologically, chemically, and immunologically to identify and target PC-affected sites for site-specific drug delivery. The strategic payload delivery capability of exosomes enhances the bioavailability and specificity of chemotherapeutic drugs. However, significant challenges remain in the clinical application of exosomes as drug carriers and biomarkers. This review summarizes the current understanding of the role of exosomes in PC development, contribution to metastasis, immunomodulation, and chemoresistance in PC. It emphasizes the therapeutic potential in tune with site-specific drug delivery and diagnostic applications of exosome-associated molecular signatures in PC detection.

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