The Role of Exosomes in Pancreatic Cancer From Bench to Clinical Application: An Updated Review

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most dismal gastrointestinal malignancies with an overall 5-year survival rate of 8%–9%. The intra-tumor heterogeneity and special tumor microenvironment in PDAC make it challenging to develop effective treatment strategies. Exosomes are extracellular vesicles that originate from the endosomes and have a diameter of 40–160 nm. A growing body of evidence has shown that exosomes play vital roles in tumor initiation and development. Recently, extensive application of exosomes as biomarkers and drug carriers has rendered them attractive in the field of PDAC. This review summarizes the latest progress in the methodologies for isolation, modification, and tracking of exosomes, exosome-mediated cell-to-cell communication, clinical applications of exosome as minimally invasive liquid biopsy and drugs carriers, as well as their involvement in the angiogenic regulation in PDAC. In spite of these advancements, some obstacles are still required to be overcome to use the exosome-based technologies for early diagnosis or improvement of prognosis of patients with PDAC.

Exploring the Clinical Utility of Pancreatic Cancer Circulating Tumor Cells

“…Similar to cfDNA, sensitivity in cancer-specific exosomes has been reported to range widely in PDAC patients, where 50% to 100% has been reported [23]. Exosomal markers have been identified for PDAC diagnosis, recurrence, and prognosis including miR-21, miR-451, miR-196a, miR-1246, and glypican-1 [36]. Isolation methods for exosomes, such as ultracentrifugation are currently inefficient and inconsistent, leading to difficulties in their characterization [37].…”

Exosomal microRNA in Pancreatic Cancer Diagnosis, Prognosis, and Treatment: From Bench to Bedside

“…Highly elevated levels of exosomal miR-17-5p and miR-21 were detected in serum samples of pancreatic cancer patients for the first time in 2013 [ 133 ]. Since then, several studies have explored the association of exosomal miRNAs in different stages of pancreatic cancer development [ 38 ]. In pancreatic cancer cells, Sun et al showed that IL-26 level was regulated by the exosomes loaded with miR-3607-3p secreted by natural killer (NK) cells, which suppressed disease progression in vivo [ 134 ].…”

“…The animals survived for a significantly longer time (increased overall survival rate) with no toxic adverse events [ 41 ]. These encouraging results led to a Phase I clinical trial in PDAC patients with a KRAS G12D mutation (NCT03608631) [ 38 ]. After subsequent verification of their safety and efficacy in organoid and patient-derived tumor xenograft models, it can be expected that engineered exosomes can be used as vehicles to deliver miRNAs as therapeutic agents for the targeted treatment of PDAC.…”

“…One of the major players in tumor microenvironment-associated intercellular communication is exosomes. The cargo of exosomes contains lipids, proteins, metabolites, and genetic material, including DNA, mRNA, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) [ 36 , 37 , 38 ]. Mounting evidence has revealed that exosomal miRNAs are intensely connected with various cancers, including pancreatic cancer [ 39 ].…”

Plasma Exosome-Derived SENP1 May Be a Potential Prognostic Predictor for Melanoma

“…Exosomes are small membranous vesicles ranging from 40 to 100 nm ( 26 ). They can be used as functional mediators in cell interactions leading to cancer metastasis ( 27 ). Metastasis is a complex multistep process of cancer cell invasion, vascular survival, adhesion and host organ colonization.…”