Once believed to be nothing more than cellular trash bags, extracellular vesicles (EVs), also known as exosomes, are now being recognised for carrying valuable genetic material. This has prompted researchers to see if these tiny vesicles could be harnessed for non-invasive diagnosis and monitoring of diseases like cancer and osteoarthritis.
A new technology, dubbed ExoGAG, promises an easy way to isolate DNA, mRNA, and miRNA that are present inside exosomes extracted from blood or urine samples. Utilizing this technology, the presence of genetic mutations and other disease-associated biomarkers can be detected, offering valuable insights for early diagnosis and monitoring of diseases
New possibilities for disease detection
EVs create a protective shell around DNA and RNA, preventing their degradation and providing a stable structure for analysis.
“EVs are stable, specific, and can be detected with just a small amount of blood; they offer a promising avenue for improving cancer diagnosis and treatment,” says Dr Bahnisikha Barman, a research instructor at the Cell and Extracellular Vesicle Lab at Vanderbilt University School of Medicine in the US.
Moreover, EV-based analysis may provide precise and comprehensive information about parent tumours using a non-invasive approach. This could help clinicians identify specific therapy in a personalised manner and significantly improve outcomes.
“The most interesting feature of EVs is that they are not just a single biomarker. EVs from tumour cells come with a multimolecular package with a variety of disease-associated biomolecules such as DNA, RNA, proteins, and lipids,” says Dr Abu Sina, a visiting research fellow at The Herbert Irving Comprehensive Cancer Center at Columbia University in New York.
This contrasts with traditional methods for cancer diagnosis that involves checking for tumour markers or taking a biopsy of the tumour itself. These methods have limitations – tumour markers can be non-specific, and biopsies are invasive and can be difficult to perform depending on the location of the tumour.
EVs offer a non-invasive alternative that is highly specific and can provide a wealth of information about the parent tumour, without the need for pricking or other invasive procedures.
Detecting mutations in DNA
In a study at the Translational Medical Oncology Group in Spain, researchers used ExoGAG to diagnose pancreatic cancer. They did this by isolating EVs from plasma samples of individuals with pancreatic cancer and extracted and analysed the DNA to detect point mutations associated with several types of cancer.
By detecting the KARS mutations (a class of genes that, when mutated, can cause normal cells to become cancerous) in EV DNA, which are commonly found in pancreatic cancer, the researchers were able to diagnose the disease with an accuracy of 80 per cent. This was a significant improvement over traditional methods, which often have lower accuracy rates and can be invasive.
Point mutations are changes in a single letter of the DNA that can significantly affect the function of the encoded protein.
Diagnosing prostate cancer
EVs can also carry RNA molecules that provide valuable information about gene expression.
The same group of researchers from the Translational Medical Oncology Group in Spain also found that analysing RNA extracted from EVs could serve as a non-invasive diagnostic tool for prostate cancer and a means to track its progression.
They found that specific genes were found to be expressed differently in those with metastatic prostate cancer compared to those with benign prostatic hyperplasia (BPH), and these genes were linked to the cancer’s aggressiveness.
Analysing miRNAs from EVs of individuals with cancer, researchers found that higher miRNA levels may lead to poor treatment response compared to those with lower levels.
Therefore, these miRNAs could potentially serve as diagnostic and prognostic biomarkers for cancer. Further studies are needed to validate these findings and determine the miRNA’s clinical utility as biomarkers.
The future of cancer screening
This exciting research is opening a new frontier in cancer diagnosis and treatment. The researchers believe that their findings could be applied to other types of cancers as well and that EV analysis could ultimately revolutionise the field of liquid biopsy.
“Although current EV-based cancer tests are mostly based on protein, lipid, or miRNA, it is not far to see other EV-based tests in the clinic providing mutations and gene expression profiles of [those with] cancer,” says Dr Sina, who is an expert in the field.
Furthermore, EVs are known to cross the blood-brain barrier and could be used for clinical purposes in dealing with neurological disorders adds Dr Barman.
Need for regulatory approvals
For EV-based liquid biopsies to become widely accepted in clinical practice, it must meet criteria such as high specificity and sensitivity. There are already companies such as Biological Dynamics and BCAL Diagnostics that have made progress in developing exosome-based cancer diagnostics.
However, experts say that regulatory approvals could take some time, slowing down the adoption of EV-based diagnosis. Their best estimate for when the technology could become widely available is five to ten years.
“The most important parameters that any EV-based liquid biopsy needs to meet is an above 90 per cent specificity and 70 per cent sensitivity in more patients,” adds Dr Sina. While some studies have shown promise in meeting these criteria, they have been done on a smaller scale.
But despite these challenges, researchers remain hopeful that EV-based liquid biopsies will revolutionise cancer diagnosis and monitoring. They stand to offer a less invasive and potentially more accurate approach to detecting different types of cancer.
