In a world where cancer remains one of humanity's most formidable diseases, scientists have turned their attention to microscopic vesicles that may hold the key to early diagnosis and effective treatment of malignant tumors.
Imagine an army of invisible couriers that tumors send throughout the body. These tiny messengers prepare new footholds for metastases, lull the immune system into complacency, and provide the tumor with resources. Exosomes — microscopic extracellular vesicles measuring 30-150 nanometers — this is what these couriers look like under a microscope 1 6 .
Discovered in the 1980s, exosomes were long considered simply "garbage containers" — a means for removing unnecessary cellular components. Only in the last two decades have scientists realized their fundamental role in intercellular communication, especially in the context of cancer 9 .
Exosomes are microscopic vesicles with a lipid shell that are secreted by almost all cell types, including cancer cells. They form inside the cell in specialized structures — multivesicular bodies — and are then released into the intercellular space, carrying "messages" in the form of proteins, lipids, and nucleic acids 4 7 .
Exosome biogenesis is a complex process regulated by various molecular mechanisms, including the ESCRT system (endosomal sorting complexes required for transport) 4 . Interestingly, cancer cells secrete exosomes in significantly larger quantities than healthy cells, making them promising markers for diagnosis .
Each exosome carries a unique molecular cargo that reflects the physiological state of the parent cell.
Each such vesicle contains a unique set of molecules that reflects the physiological state of the parent cell and can influence the behavior of recipient cells. Upon entering other cells, exosomes can transfer oncogenic signals, altering the function of healthy cells and promoting tumor progression 6 7 .
Exosomes secreted by tumor cells have a dual nature — they can both promote cancer development and become a powerful tool in the fight against it.
One of the most promising directions in modern oncology is the development of liquid biopsy methods — non-invasive cancer diagnosis using biological fluids. Exosomes are ideally suited for this role since they are present in blood, urine, saliva, and other body fluids in large quantities 6 9 .
Higher sensitivity of exosome-based diagnostics compared to traditional tumor markers in early-stage cancer detection
Simple blood draw is sufficient instead of tissue biopsy
Exosomes reflect changes at the molecular level before clinical manifestations
Possibility of repeated monitoring of disease course and response to therapy
Exosomes carry information about the entire tumor, not just a biopsied part 9
| Method | Sensitivity | Invasiveness | Monitoring Capability | Informativeness |
|---|---|---|---|---|
| Traditional Biopsy |
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Local |
| CT/MRI |
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Anatomical |
| Tumor Marker Analysis |
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Systemic |
| Exosomal Diagnostics |
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Molecular and Systemic |
Scientists are actively studying various components of exosomes to identify the most informative diagnostic markers. Among them:
CD63, CD81, EpCAM, EGFR — used to identify tumor exosomes 9
Carry genetic information about the tumor 6
Particular interest is the detection of PD-L1 protein in exosomes, which plays a key role in suppressing anti-tumor immunity. Research shows that the level of exosomal PD-L1 correlates with disease aggressiveness and can serve as a prognostic marker 9 .
| Direction | Mechanism of Action | Development Stage | Progress |
|---|---|---|---|
| Chemotherapy Delivery | Targeted transport of drugs to tumor cells | Preclinical Studies |
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| Gene Therapy | Delivery of microRNA and other regulatory RNAs | Preclinical Studies |
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| Immunotherapy | Inhibition of PD-1/PD-L1, activation of anti-tumor immunity | Early Clinical Studies |
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| Cancer Vaccines | Presentation of tumor antigens to the immune system | Preclinical Studies |
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Engineered exosomes are one of the most promising directions. Scientists have learned to modify natural exosomes by filling them with chemotherapeutic drugs (paclitaxel, docetaxel) or therapeutic nucleic acids capable of suppressing oncogenes 5 .
Particular interest is in mesenchymal stem cell (MSC) exosomes, which demonstrate natural tropism to tumor tissue and can be used for targeted delivery of anti-tumor agents. Research shows that MSC-Exos can suppress prostate cancer growth by modulating the immune response and influencing tumor cells through microRNA transfer 5 .
To understand how scientists study exosomes, consider a key experiment on isolating exosomes directly from tumor tissue, described in the Journal of Visualized Experiments 2 .
Researchers developed a protocol that allows obtaining exosomes under conditions as close to natural as possible, without using enzymatic tissue digestion that could damage the fragile vesicles.
Tumor was extracted from a mouse model after four weeks of growth, treated with 75% alcohol for sterilization
Tumor was washed with chilled phosphate buffer (PBS) to remove blood and fat, then cut into small fragments approximately 1 mm³ in size
Tumor pieces were placed in serum-free medium and incubated on a shaking table at 37°C for exosome release
After 24 hours, the medium with released exosomes was collected and centrifuged to remove cellular debris
Exosomes were concentrated and purified using ultracentrifugation or chromatographic methods
This method allowed obtaining exosomes that more accurately reflect their natural state in tumor tissue than exosomes isolated from cell cultures. Analysis showed that such exosomes maintain their structural integrity and biological activity.
| Reagent/Method | Purpose | Application in Research |
|---|---|---|
| Serum-Free Medium | Culturing tumor tissues | Ensuring exosome release without contamination by serum vesicles |
| Ultracentrifugation | Isolation and purification of exosomes | Concentration of exosomes from culture medium |
| Flow Cytometry | Analysis of surface markers | Identification of exosomes by CD9, CD63, CD81 markers |
| Western Blotting | Detection of specific proteins | Confirmation of tumor marker presence |
| Electron Microscopy | Visualization of exosomes | Confirmation of size and vesicle morphology |
| Next-Generation Sequencing | Analysis of nucleic acids | Determination of RNA content in exosomes |
Despite impressive progress, serious challenges must be addressed before exosomal technologies can be widely implemented in clinical practice. The main problems are: 3 4 5
Nevertheless, the pace of research in this area is impressive. According to PubMed, the number of publications on "exosomes and cancer" is growing rapidly, peaking in 2023 3 .
Tumor cell exosomes are not just the body's "message in a bottle," but a sophisticated communication system that opens new horizons in oncology. From "liquid biopsy" for early diagnosis to targeted drug delivery — these microscopic vesicles demonstrate colossal potential for transforming approaches to diagnosing and treating malignant diseases.
"Exosomes offer significant potential for future cancer therapy, and further research should be aimed at improving production efficiency and facilitating clinical translation" 4 .
Although there is still a long way to go before the widespread clinical application of exosomal technologies, it is already clear that they could form the basis for the personalized oncology of the future, where treatment will be tailored based on the unique molecular portrait of each patient's tumor.
Perhaps these tiny vesicles will help us achieve ultimate victory in the fight against cancer.