Researchers from WUR and University of Twente have taken the first steps towards a new method to detect cancer in blood. An analysis of one drop of blood may be sufficient in the future to detect cancer at a very early stage.
Cells communicate with one another by means of vesicles, Extracellular Vesicles (EVs). Tumour cells also release these vesicles which are then called tumour-derived Extracellular Vesicles (tdEVs). ‘Previous research shows that the number of tumour-derived vesicles in the blood is linked to the probability of patient survival’, says Pepijn Beekman, PhD candidate at Organic Chemistry. ‘This means they aren’t only interesting for diagnostics, but also for monitoring whether a treatment is successful.’ Together with Agustin Enciso-Martinez, PhD candidate at University of Twente, Beekman has developed a chip that can be used to detect tumour-derived vesicles.
One drop of blood
'There are already tests to detect cancer in blood by searching for cancer cells or cancer cell DNA', Beekman explains. 'But detection is still very difficult, in particular in the early stages. As the concentration of cancer cells is generally very low, you have to take lots of test tubes of blood to find one cancer cell.’ He believes that the tumour-derived vesicles may offer a solution as they are present in much larger numbers. 'This means you can obtain a huge amount of information from one drop of blood. This was not possible with existing analysis methods. Blood contains a lot of other small particles and until now it was very difficult to identify the tumour-derived vesicles.'
This new method allows the capture of tumour-derived vesicles in a reliable manner and allows researchers to isolate them from the other particles. The researchers used a chip with antibodies on it that, like the pieces of a puzzle, only fit on tumour-derived vesicles. They tested this method on tumour-derived vesicles from prostate cancer cells. As the vesicles are too small to be visible under a normal microscope, they used different methods of analysis to obtain highly detailed information from the tumour-derived vesicles, such as Raman spectrometry. ‘Because each vesicle is slightly different’, explains Beekman. By combining different analysis methods, the researchers were able to unravel the unique fingerprint of a tumour-derived vesicle. They can use this information to develop diagnostic tests.
Beekman: ‘The problem is that each time you change instrument to make a new analysis, you have to find exactly the same particle on the chip again. It’s like searching for a needle in a haystack.’ Then he came up with a solution: inspired by the parking garage at Schiphol, Beekman divided the microchip into “parking spaces” including the symbols that he had “grafted” into the chip. ‘This meant I knew, for example, that I had looked at that specific particle at Klomp A9.’
In the future Beekman wants to test the method on blood samples from patients. ‘Ultimately we hope that there will be a test that only requires one drop of blood. Then, for example, you’ll be able to see at a very early stage whether someone has cancer, even before tumours are visible on scans, and determine which is the best treatment.’ But it will certainly be another five years before the first clinical trials can be carried out.
The research was published in the journals Lab on a Chip and Nanoletters. The study is part of the Cancer-ID programme which is co-funded by the Netherlands Organisation for Scientific Research (NOW).