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Review
. 2022 Oct 14;20(1):446.
doi: 10.1186/s12951-022-01641-0.

Cancer-derived small extracellular vesicles: emerging biomarkers and therapies for pancreatic ductal adenocarcinoma diagnosis/prognosis and treatment

Wei Zhang  1 , Douglas H Campbell  2 , Bradley J Walsh  2 , Nicolle H Packer  1 , Dingbin Liu  3 , Yuling Wang  4
Affiliations
Review

Cancer-derived small extracellular vesicles: emerging biomarkers and therapies for pancreatic ductal adenocarcinoma diagnosis/prognosis and treatment

Wei Zhang et al. J Nanobiotechnology. .

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers worldwide with high mortality, which is mainly due to the lack of reliable biomarkers for PDAC diagnosis/prognosis in the early stages and effective therapeutic strategies for the treatment. Cancer-derived small extracellular vesicles (sEVs), which carry various messages and signal biomolecules (e.g. RNAs, DNAs, proteins, lipids, and glycans) to constitute the key features (e.g. genetic and phenotypic status) of cancer cells, are regarded as highly competitive non-invasive biomarkers for PDAC diagnosis/prognosis. Additionally, new insights on the biogenesis and molecular functions of cancer-derived sEVs pave the way for novel therapeutic strategies based on cancer-derived sEVs for PDAC treatment such as inhibition of the formation or secretion of cancer-derived sEVs, using cancer-derived sEVs as drug carriers and for immunotherapy. This review provides a comprehensive overview of the most recent scientific and clinical research on the discovery and involvement of key molecules in cancer-derived sEVs for PDAC diagnosis/prognosis and strategies using cancer-derived sEVs for PDAC treatment. The current limitations and emerging trends toward clinical application of cancer-derived sEVs in PDAC diagnosis/prognosis and treatment have also been discussed.

Keywords: Cancer diagnosis/prognosis; Cancer treatment; Extracellular vesicles; Pancreatic cancer.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Fig. 1
Fig. 1
Biogenesis and identification of small extracellular vesicles (sEVs). sEVs originate from the endosomal pathway by the formation of endosomes and MVBs. When MVBs fuse with cell membrane, sEVs are released into extracellular milieu. sEVs are composed of a lipid bilayer vesicle containing nucleic acids, proteins, lipids, glycans, and other small molecules
Fig. 2
Fig. 2
Molecular analysis of components in/on sEVs for PDAC diagnosis/prognosis. PDAC-derived sEVs circulating in blood can be enriched by techniques such as ultracentrifugation. Molecular components including RNAs, DNAs, proteins, lipids and glycans can be analyzed to generate the unique molecular signature for PDAC diagnosis/prognosis
Fig. 3
Fig. 3
Schematic of the formation and release of sEVs. MVB biogenesis is associated with ESCRT-dependent and ESCRT-independent pathways, agents such as ROCK, RAB, SNARE, Ca2+ affect the release of sEVs from cells
Fig. 4
Fig. 4
Strategies of using cancer-derived sEVs for drug delivery. Chemotherapy drugs, nucleic acids and/or proteins can be loaded into sEVs by direct or indirect methods
Fig. 5
Fig. 5
Effects of cancer-derived sEVs on immune cells and therapeutic strategies for cancer treatment by immunotherapy. Cancer-derived sEVs contain immunosuppressive and immunostimulatory molecules, which can be used to activate immune cells. Loading immune drugs into sEVs or inhibition of cancer-derived sEV secretion are two other strategies for immunotherapy
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