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Review
. 2022 Mar 25;23(7):3620.
doi: 10.3390/ijms23073620.

Exosomes in the Treatment of Pancreatic Cancer: A Moonshot to PDAC Treatment?

Stavros P Papadakos  1 , Nikolaos Dedes  1 , Alexandros Pergaris  1 , Maria Gazouli  2 , Stamatios Theocharis  1
Affiliations
Review

Exosomes in the Treatment of Pancreatic Cancer: A Moonshot to PDAC Treatment?

Stavros P Papadakos et al. Int J Mol Sci. .

Abstract

Pancreatic Ductal Adenocarcinoma (PDAC) constitutes a leading cause of cancer death globally. Its mortality remains unaltered despite the considerable scientific progress made in the fields of diagnostics and treatment. Exosomes comprise of small extracellular vesicles secreted by nearly all cells; their cargo contains a vast array of biomolecules, such as proteins and microRNAs. It is currently established that their role as messengers is central to a plethora of both physiologic and pathologic processes. Accumulating data have shed light on their contributions to carcinogenesis, metastasis, and immunological response. Meanwhile, the advancement of personalized targeted therapies into everyday clinical practice necessitates the development of cost-efficient treatment approaches. The role of exosomes is currently being extensively investigated towards this direction. This review aims to summarize the current pre-clinical and clinical evidence regarding the effects of exosomal applications in the timely diagnosis, prognosis, and therapeutic management of pancreatic cancer.

Keywords: biomarkers; diagnosis; exosomes; pancreatic cancer; prognosis; therapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The construction of artificial exosomes (A,B), the “top-down” strategy: forced passage through porous membranes or microfluidic devices, nitrogen cavitation; cell membrane blebbing. (C) The supramolecular construction of artificial exosomes with biohybrid technologies (D), the “bottom-up” methodology: the supramolecular construction of complex structures from basic components. Created with BioRender.com.
Figure 2
Figure 2
The PDAC microenvironment. Created with BioRender.com.
Figure 3
Figure 3
The contribution of the PDAC microenvironment to the generation of drug resistance. (A) GEM-treated PDAC cells secrete miR-155 through exosomes enhancing the antioxidant capacity of cancer cells (through the downregulation of SOD2 and CAT), disrupting the activation of GEM (through the downregulation of DCK) and cellular stress-sensing systems (by upregulating TP53INP1). (B) GEM-treated CAFs exosomally secreted miR-106b, miR-146a, and Snail, all of which mediate their intrinsic resistance to GEM. (C) The M2-derived exosomally excreted miR-365 increased the intracellular NTP pool and the CDA. (D) GEM-resistant cancer stem cells secreted through exosomes miR-210 induced drug resistance through mTOR signaling potentiation. (E) The knockdown of EPHA2 in drug-resistant cells decreased their efficiency in transmitting GEM resistance. Created with BioRender.com.
See this image and copyright information in PMC

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