In the weekly ‘follow-up’ section we present a sequel to last week’s best-read article. This week it was about Swiss researchers who are developing a special blood test that can detect more than fifty different types of early onset cancer in the blood.

Tumors release DNA into the blood even before they spread or lead to cancer. But other cell types also secrete this so-called cell-free DNA (cfDNA) in the blood. This makes it difficult to determine which cell-free DNA comes from tumors. Which is something that Swiss researchers have discovered. Their blood tests analyze the chemical changes in DNA, known as “methylation” which normally controls gene expression. “Abnormal methylation patterns and the resultant changes in gene expression can contribute to tumor growth, Which means that these signals in the cfDNA have the potential to detect and localize cancer,” says the study. This was published in the leading cancer journal Annals of Oncology.

Pepijn Beekman and Dilu Matthew from ECsens are working on an ultra-accurate biosensor that works with nano-electrodes. The aim of their ‘lab on a chip’ is to check whether cancer treatments work and then adjust them accordingly to each individual. However, it should also be possible to use this chip to detect this disease in its early stages in future.

Beekman clarifies how they have placed antibodies on electrodes which recognize certain biomarkers. “We know these substances don’t belong in a healthy person’s blood. If a biomarker like that gets close to an antibody, it sticks to the sensor and we are able to read it.”

Vast jungle of all kinds of substances

The sensor is able to detect the biomarkers in the blood Using just a tiny bit of blood. “You have to imagine that blood is a vast jungle of all kinds of substances. The art of a biosensor is its ability to detect low concentrations of biomarkers that are also in the blood. Additionally, the sensor should not react to other substances that may look like these, but which aren’t the same. This is referred to as selectivity. Our sensor is not only ultra-accurate, it’s also very selective.”

Beekman: “The concentration of biomarkers in the blood drops dramatically during the early stages of cancer, as you can see in this Swiss study. In order to successfully detect this, you need techniques that are even more sensitive than what is currently available. Our technique has that potential.”

Although, according to him, diagnosing cancer at an early stage is not something that can be done by a company as young as ECsens. “In order to monitor everyone at risk of a disease, you need to set up large-scale population screening. For this, you need access to logistics channels that are only available to established multinationals. Also, the confidence in your technology needs to be so high that radiologists and oncologists accept it before they go on to use it en masse. Our technology hasn’t yet reached that stage of development. That’s why we’re now focusing on monitoring treatments.”

Picking up subtle signs

A doctor is able to assess whether a treatment is effective by measuring the amount of biomarkers in patients’ blood. “Doctors now check with an MRI or CT scan to see if a tumor is shrinking. But these scans can give a distorted picture and may not always accurately measure a tumor. There may be some tumors that are too small to detect, known as micrometastases. It may also look as if a tumour is shrinking while nothing has actually changed. Or the other way around, it may look as if a treatment is not working, but is in fact effective. These are often very subtle signals that you could pick up with the help of blood analysis.”

The technology is also a lot cheaper than all the other scans that patients currently need for treatment. “Our method would be about five times cheaper than the other scans. And since doctors can see more quickly that a treatment is not effective, they could switch to another medicine much sooner. What’s more, giving a small amount of blood is less invasive and enables you to keep an eye on patients more often and with greater accuracy.”

Read more about ECsens here

The next step is to test these chips on patients. Originally, ECsens was supposed to start a clinical trial during this period. However, due to the outbreak of the corona virus, this has been suspended for the time being. “We want to prove that our technology works by using patient samples. The next challenge is to further develop this and to engineer a fool proof system so that lab technicians can easily work with it. However, the lab at the University of Twente is currently only available for urgent research related to corona. So, we need to be patient for a little while longer.”

Although the technology may be suitable for detecting cancer earl-onset cancer in the future, for now ECsens is mainly working on monitoring patients’ courses of treatment. “Generally speaking, the challenge for clinicians is to find biomarkers. We are developing platforms that can reliably detect these biomarkers. Therefore, we need clinicians to let us know exactly what our system should detect. So, we know what we are focusing on for the proof of concept, but there are different biomarkers for many other specific types of cancer. But for early phase diagnostics, I think the same biomarker that we are using now would also work fine.”