"Look, you can see here how a cancer cell detaches itself from the tumour in a breast, travels through the blood stream and spreads into the liver." The colours displayed on the computer screen are strangely beautiful even though they represent a life-threatening situation. Professor Jacco van Rheenen, biophysicist and group leader at the Hubrecht Institute and Professor of Intravital Microscopy at the University Medical Center Utrecht (UMC), is the only professional in the world who has the ability to create these images. Armed with the ERC Consolidator Grant that has just been awarded to him, he will now be able to investigate why chemotherapy has a very undesirable effect on a small number of tumour cells. These cells do not die after the chemo course has been completed; rather the opposite is true: they become active.
Usually, a number of different treatments will be used against a tumour: a surgical procedure to remove the original tumour, possibly in combination with radiotherapy, followed by a course of chemotherapy specially designed to stop the cancer from spreading. This treatment is often enough to halt the cancer. But unfortunately, in a number of cases, it returns a number of years later, often in a more aggressive form. By the time a patient has a check up, there are many metastases elsewhere in the body. Van Rheenen says: “Now that people are living longer, recurring cancer is becoming an ever greater problem. My question: why is this?”
The combination of medicines used in chemotherapy focus on a mix of the most common tumour cells. However, a very small proportion of the tumour cells are resistant and become active again, often after a period of time. "In recent years, we have developed a technique for producing images of these metastases. We can monitor the tumour cells both during and after the chemotherapy. One thing we have observed is that the surviving tumour cells become more active after a course of chemotherapy. They become agile and start to travel and multiply. The cancer cells that survive chemo seem to become stem-cells. Stem cells are cells that are able to divide infinitely." As a result, the tumour spreads very quickly indeed at a later stage. Van Rheenen says: "We can label the cells to make them change colour when this happens. The next question is then which type of cells is involved? If we can see how the cellular mechanism works 'live', we will hopefully be able to prevent this from happening in the future."
He explains that the residual material from the cells killed during chemotherapy is harmful too. "The dead cells disintegrate into a large number of little vesicles which contain RNA and DNA. Once the cancer cells are dead, our immune cells clear away what is left. They absorb the vesicles along with their harmful properties." And that's not all. "When immune cells arrive, they send out signals. There are a number of reasons for this. One of these is to activate the division of surrounding cells, so that the space created is quickly closed again. Unfortunately, this also activates the remaining tumour cells."
The research to be carried out requires a combination of technical, biological and medical knowledge. Van Rheenen says: "When I was studying Biology in 1996, I was fascinated by the tests being done on Herman the bull. Later, when I was working on my PhD at the Netherlands Cancer Institute (Nederlands Kankerinstituut), I learned how to film cells in vitro. In the US, I developed a very precise method that made it possible to view images of tumour cells in living tissue. Back at Utrecht University, I can successfully follow metastases too." The research team uses highly advanced infra-red microscopes. "Infra-red rays have a long wavelength, which enables them to penetrate through tissue. I position two rays to converge precisely at the area to be examined. The level of radiation applied here must be as low as possible to avoid any damage."
The ERC research that Van Rheenen and his team will do will focus initially on breast cancer and metastases in the liver. They will look for mechanisms that are likely to apply to other types of tumour too. The objective is to deactivate the basic mechanism. This could be done, for example, by blocking the signals from the immune cells or by desensitising the remaining tumour cells. "This is exciting research and we are making new discoveries on a regular basis. However, our ultimate goal is to make patients better."
By: Youetta Visser