Utility of Exosomes in the Diagnosis and Treatment of Pancreatic Adenocarcinoma

Abstract

Pancreatic cancer is the most common lethal cancer, with annual incidence and mortality rates being approximately equal. This dismal prognosis can be attributed to late diagnosis making the cancers unresectable. These cancers respond poorly to chemotherapy and radiation, and surgical resection remains the most effective treatment available. Diagnostic tests that are sensitive, specific, and capable of early detection are urgently needed and would significantly impact upon pancreatic cancer treatment and outcomes. Exosomes, small membrane-bound vesicles which are fairly uniform in size (approximately 30–100 nm in diameter), contain messenger RNA, microRNA (miRNA), and proteins. They are ubiquitous and stable in most body fluids and exosomal miRNAs are also resistant to degradation by RNAses and DNAses. Expression profiles of serum exosomal miRNAs display sensitivity and specificity in the detection of pancreatic adenocarcinoma. Markers of pancreatic cancer-initiating cells are also expressed on serum exosomes. Exosomes exhibit key functions in addition to their distinct structural properties: they are involved in immune system modulation via the transfer of antigenic proteins, and through protease activity they modulate the extracellular environment prior to metastasis. Exosomes are being studied as potent gene delivery tools and dendritic cell exosomes are already used as cancer vaccines. This review focusses on the current state of exosomal research, particularly in relation to their applicability as diagnostic and therapeutic tools for patients with pancreatic adenocarcinoma.

Keywords

• adenocarcinoma
• biomarkers
• diagnosis
• exosomes
• pancreatic
• vesicles