Tumor extracellular vesicles as biomarkers for precision medicine

Extracellular vesicles (EVs) have attracted considerable interest as possible biomarkers for a variety of diseases, including cancer. EVs are small membrane-bound vesicles released into the extracellular space by cells, including tumor cells. They carry a variety of molecular cargo, such as proteins, nucleic acids (DNA, RNA, and microRNAs), lipids, and metabolites, and are crucial in the transfer of these biomolecules to recipient cells, allowing them to communicate with one another.

Role of Tumor EVs in Cancer

Tumor extracellular vesicles (EVs) have been widely investigated in cancer, and there is compelling evidence that they play a role in different aspects of tumor biology.

Tumorigenesis

Tumor EVs have been shown to transfer a variety of cargo molecules (specific oncogenic proteins, mutated DNA, RNA transcripts, and miRNAs) that can influence the behavior and function of recipient cells, modulating processes such as angiogenesis, immune evasion, tumor growth, and metastasis.

Metastasis and pre-metastatic niche formation

Tumor EVs have been implicated in the formation of pre-metastatic niches and metastatic lesions in distant organs during metastasis by modifying their cellular composition, inducing immune suppression, and creating a favorable environment for tumor cells to colonize, promoting angiogenesis.

Immune modulation and evasion

Tumor EVs can transport immunosuppressive molecules, suppressing immune responses and promoting immune tolerance. They can also inhibit immune cell function, weakening their anti-tumor activity. Tumor EVs may additionally transfer tumor antigens to antigen-presenting cells (APCs), which promotes immune recognition and T-cell priming.

Diagnostic and prognostic biomarkers

Tumor EVs contain specific molecules such as mutated DNA, oncogene RNA transcripts, and proteins linked with tumor progression and treatment resistance, which can serve as promising diagnostic and prognostic biomarkers for early cancer detection.

These are only a few examples of evidence that tumor EVs play a role in cancer. Ongoing research is underway to better understand the mechanisms and functional implications of tumor EVs, as well as their potential as biomarkers for targeted therapies and drug delivery vehicles in cancer..

Tumor EVs as Biomarkers of Cancer in Precision Medicine

Precision medicine in cancer refers to an approach to cancer diagnosis, treatment, and prevention that considers the individual characteristics of each patient and their tumor. It aims to deliver targeted and personalized therapies based on the specific genetic, molecular, and clinical features of the patient and their disease.

Tumor EVs have a few advantages that make them appealing biomarkers of cancer:

Abundance

Tumors release more EVs than normal cells, resulting in an increased presence of tumor specific EVs in body fluids such as blood, urine, saliva, and tumor interstitial fluid (TIF).

A reflection of parent cells

As EVs carry proteins, nucleic acids, and lipids from the parental cell, their cargo is representative of parental cells. EV cargo is different in various cancer types, making them potential biomarkers of cancer.

Early detection

Tumor EVs carry specific molecules derived from the tumor cells, including mutated DNA, RNA transcripts, and proteins associated with tumor progression. By analyzing the cargo of tumor EVs, it may be possible to detect cancer at an early stage, even before clinical symptoms manifest. Early detection of cancer can significantly improve patient outcomes by enabling timely intervention and treatment initiation.

Tumor EVs, as a promising source of biomarkers, can thus help accelerate the development of precision medicine in cancer in the following ways:

Real-time and dynamic information

As EVs are continuously released by tumor cells, they provide an ongoing snapshot of the tumor's status and response to treatment. This dynamic information can be leveraged to make informed treatment decisions, including the selection of targeted therapies or clinical trial eligibility.

Prognostic and predictive information for treatment selection

Tumor EVs carry specific molecules derived from the tumor cells, such as mutated DNA, RNA transcripts, and proteins associated with tumor progression, poor prognosis, resistance to treatment, or therapeutic. By analyzing the cargo of tumor EVs, clinicians can gain insights into the genetic and molecular profile of the tumor, helping to guide treatment selection. For example, the presence of specific genetic mutations or the expression of certain proteins in tumor EVs may indicate the suitability of targeted therapies or immunotherapies for a particular patient.

Understanding tumor heterogeneity

Tumors are often heterogeneous, with diverse cell populations carrying distinct genetic and molecular characteristics. Tumor EVs can provide insights into this heterogeneity by capturing the cargo from different subclones within the tumor. By studying the cargo of tumor EVs, researchers and clinicians can gain a better understanding of tumor subtypes, clonal evolution, and mechanisms of treatment resistance. This information can help tailor treatment strategies to address the specific characteristics of individual tumors.

Monitoring treatment response

Tumor EVs can provide a real-time snapshot of the tumor's genetic and molecular changes during treatment. By analyzing the cargo of tumor EVs longitudinally, clinicians can monitor treatment response and detect the emergence of resistance or disease progression. This information can guide treatment modifications and help optimize therapy for individual patients.

Drug delivery and therapeutics

Tumor EVs can be harnessed to carry therapeutic payloads, such as drugs, siRNAs, or gene therapies, and specifically target tumor cells. By utilizing tumor EVs as delivery vehicles, precision medicine approaches can enhance the specificity and efficacy of treatments while minimizing off-target effects

Challenges in Harvesting Tumor EVs

While tumor EVs have the potential to accelerate precision medicine, the blood and urine from which they are harvested are not ideal sample sources compared to other tumor EV sample sources.

Tumor EVs in blood or urine are typically present in low concentrations and are diluted by a large number of EVs originating from non-tumor sources. Also, Tumor EVs in the blood or urine must travel through the bloodstream, where they may undergo modifications and lose some of their cargo, limiting their capacity to represent the tumor's native surroundings and heterogeneity.

Furthermore, the conventional techniques used for the isolation and characterization of tumor EVs present some challenges related to EV purity, heterogeneity, and the presence of contaminants that affect the analysis and interpretation of results.

To address these challenges, researchers are actively exploring and developing alternative and improved techniques.

Overcoming the Challenges in Harvesting Tumor EVs

Tumor EVs derived from TIF have gained popularity in recent years due to several reasons. TIF tumor EVs are closer to the tumor microenvironment, where crucial interactions between tumor cells, stromal cells, and immune cells take place. Because TIF surrounds and permeates tumor tissue, the EVs released into it can carry molecular cargo that reflects the dynamic molecular changes and communication within the tumor microenvironment. TIF-derived tumor EV analysis can reveal information about tumor-stroma interactions, immunological modulation, and other microenvironmental factors influencing tumor behavior.

Targeted Bioscience’s Targeted EV™ Interstitial Fluid and Extracellular Vesicle Isolation Kit is designed to meet researchers’ need for purity, speed, and reproducibility. The kit offers a highly efficient method to harvest EVs from the TIF without affecting the viability or morphology of the tissue cells. The one-step protocol extracts EVs of all subtypes efficiently, providing highly reproducible enrichment of EVs and delivering unique molecular information that could reveal previously unknown insights. Targeted Bioscience’s innovative solutions are helping towards accelerating translational and clinical research to advance precision medicine. To learn more about Targeted Bioscience, click here.

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