Aesop, the Greek fabulist and storyteller, coined the phrase “good things come in small packages.” Now a team of researchers from Memorial Sloan Kettering (MSK) and Weill Cornell Medicine report that extracellular vesicles and particles (EVPs)—tiny packages of materials released by tumors and immune cells—may serve as biomarkers for diagnosing early-stage cancer.

Their study, “Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers,” is published in the journal Cell.

William Jarnagin, MD, MSK surgeon chief, hepatopancreatobiliary service, stated, “One of the holy grails in cancer medicine is to diagnose early cancer in a patient based on a blood test. This research is a proof-of-principle study; much more work is needed before it can be used as a screening tool. But ultimately, it would be fantastic if we could use this approach to find cancer in someone before they had symptoms.”

Previous work on liquid biopsies has focused on the detection and analysis of cancer genes that are released by cancer cells into the blood. Using liquid biopsies as a screening tool to detect previously undiagnosed cancer is still experimental.

The new study focuses on examining proteins contained in EVPs rather than analyzing genes. David Lyden, MD, PhD, the Stavros S. Niarchos professor in pediatric cardiology, and professor of pediatrics and of cell and developmental biology at Weill Cornell Medicine, studies EVPs in his lab, and has found that tumors may release EVPs as a way to prepare other parts of the body to receive cancer cells when they spread.

“There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of EVPs in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids,” the researchers wrote.

EVPs are membrane-enclosed particles that act as carriers of active molecules like RNA, DNA, proteins, metabolites, and lipids. EVPs can mediate intercellular signaling, modulate stroma tissue, or even regulate inflammatory and immune responses once they are secreted. They can also cross barriers, such as the blood-brain barrier, and get internalized into cells with a high degree of specificity.

“One test tube of blood contains billions of EVPs,” added Lyden. “This means a person with cancer has an abundant source of cancer-associated EVPs that clinicians could assess for diagnosis.”

While liquid biopsies provide noninvasive techniques for early cancer detection and monitoring of disease progression, they also have disadvantages, including false-positive and false-negative results and tumor microenvironmental changes.

One potential advantage researchers have found with focusing on proteins in EVPs is that it allows them to also characterize different types of cells around the tumor microenvironment. Additionally, it may help them detect changes in other tissues.

The research included samples from 18 different cancers, including breast, colon, and lung, which came primarily from MSK. There was a comparison group of samples from people who didn’t have cancer.

Through the application of machine-learning classification, researchers were able to match particular EVP protein signatures with certain types of cancer. Once the computing method was established, the team found that the computer could identify different types of cancer from the samples with a sensitivity of 95%  and a specificity of 90%.

The researchers noted that while CT and MRI scans are still needed to confirm where the tumor is located, being able to utilize a blood test to find out whether someone is at risk is a major advantage.

Looking forward, the team of researchers is validating that their lab findings with EVPs will work with additional patients.

Jarnagin noted the advantage this type of test could mean for cancers without screenings such as liver and pancreatic cancers.

“These cancers are rarely detected early and treating them as soon as possible could result in better patient outcomes,” concluded Lyden.

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