Molecular Cancer: Exosomal biogenesis, mechanism, regulation and significance of cancer treatment

Exosomes are extracellular vesicles about 30-150 nm in diameter that are secreted
by the fusion of polyfollicle bodies (MVBs) with the plasma membrane.
Since they were first visualized and described in the 80s of the 20th century, especially in the last 10 years, the field of exosome research has developed
rapidly.
Exosomes contain a variety of substances such as proteins, lipids, and nucleic acids, including messenger RNA, noncoding RNA, and DNA
.

Exosomes play a fundamental role
in maintaining homeostasis and fighting stress by exchanging functional content between cells.
Many studies have shown that exosomes are involved in a variety of protumor activities, including anti-apoptosis, metastasis, angiogenesis, immune evasion, and chemotherapy resistance
.

These features have been well reviewed from different angles, such as the type of donor cell or the category of
content.
However, the molecular mechanisms of exosome biogenesis, particularly how these mechanisms are exploited by cancer cells, have not been studied
in depth.

Image source: https://doi.
org/10.
1186/s12943-022-01671-0

Recently, researchers from the First Affiliated Hospital of Zhengzhou University published a review article entitled "Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer" in the journal Molecular Cancer, in which researchers systematically summarized the latest advances to understand the mechanism of exosome biogenesis.
and how it is regulated in the context of cancer
.
In particular, we highlight pharmacological targeting of exosome biogenesis as a promising cancer treatment strategy
.

Exosomes are well-known key vectors for cell-to-cell communication, involved in a variety of physiological and pathological processes
.
Their biogenesis involves four key steps, including cargo sorting, MVB formation and maturation, MVB transport, and MVB fusion
with plasma membrane.
Each process is regulated by the competition or coordination of multiple mechanisms, whereby different molecular cargo is divided into different exosome subpopulations, resulting in a high degree of exosome heterogeneity
.

Interestingly, cancer cells use a variety of strategies, such as abnormal gene expression, post-translational modifications, and altered signaling pathways, to regulate exosome biogenesis, composition, and ultimately function to promote cancer progression
.
Therefore, exosomal biogenesis targeted therapy is being actively explored
.

Overview of exosomal biogenesis processes

Image source: https://doi.
org/10.
1186/s12943-022-01671-0

Cancer cells use a variety of strategies to hijack exosome biogenesis mechanisms to facilitate their progression
.
Therefore, elucidating this mechanism is of great
therapeutic importance.
The International Society for Cellular Exosomes (ISEV) has highlighted the promise
of cellular exosomes as therapeutic agents.
So far, many compounds have been identified to target exosome biogenesis, and preclinical studies have revealed their therapeutic potential
.

Despite this, clinical trials are still lacking
.
Further research should assess their clinical value and side effects
.
In addition, given the role of exosomes in the tumor microenvironment, the combination of exosome-targeting compounds with other antitumor drugs, such as anti-PD-1/PD-L1 or chemotherapy drugs, may be a potential cancer treatment strategy
.
(Biovalley Bioon.
com)

References

Qing‑Fang Han et al.
Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer.
Mol Cancer.
2022 Nov 1; 21(1):207.
doi: 10.
1186/s12943-022-01671-0.