Exosomes in bile as potential pancreatobiliary tumor biomarkers

Alterations in bile secretion and its composition results in different pancreatobiliary alterations such as cholangiocarcinoma (CCA), gallbladder cancer (GBC) among others, which are usually detected in late stages and associated with discouraging rates of survival. Given the challenges of clinical detection of the biliary tract abnormalities, the search for biomarkers for detection, prevention and management of bile tract pathology is of the utmost importance. Current blood based biomarkers have low sensitivity and specificity; therefore, new alternatives must be identified and validated, principally in fluids that are in direct contact with the affected tissues such as bile. Molecules in contact with the site of the lesion have proven potentially diagnostic for biliary tract tumors and allow the discrimination of different pathologies and its stages. However, the acquisition of these molecules has some technical drawbacks, and poses obstacles that are hard to overcome during the implementation of these techniques in a clinical setting. Extracellular vesicles (EVs) such as exosomes have been suggested as messengers between distant cells and are representative of their tissues of origin. It has been shown that tumor derived exosomes carry nucleic acids and oncogenic proteins, that contribute to the microenvironment necessary for tumor progression. Accordingly, tumor derived exosomes have been the focus of research to identify potential screening biomarkers and therapeutic targets, since they don't require invasive procedures and carry not only useful information but also protect their material from extracellular enzymes and contaminants, improving molecular detection. These EVs haven't been well characterized in biliary tract cancers as its study is very recent. Nonetheless, a few studies have highlighted the role of exosomes as facilitators of these cancers' progression. The relationship between the presence and secretion of exosomes with altered expression of different molecules with diagnostic potential has been pointed out in recent studies, both in malignant diseases and benign conditions like inflammatory abnormalities. Since biliary tract pathologies are not easily detected and are often uncovered in advanced stages, overcoming the gap between basic and clinical research to identify and validate different candidate biomarkers that are present in exosomes is a decisive goal that requires large-scale multicenter studies and standardization of isolation, purification and characterization techniques.