Rob Coppes: Researches the effects of radiation used in radiotherapy for cancer in mice and rats.
“I research the effects of radiation as used in radiotherapy to cure cancer. I mainly study the effects of radiation on normal tissue. What causes the side effects that a patient experiences when a tumor is irradiated? You can essentially eliminate a tumor with radiation, but that radiation also has to pass through healthy tissue surrounding the tumor. This healthy tissue can then be damaged. Healthy tissue thus determines the dose the patient can receive, and sometimes the dose cannot reach the level needed to eliminate the tumor. But even then, tissue damage can occur to healthy tissue, which can cause significant discomfort for the patient and, in rare cases, can be fatal.
In my research, I try to unravel the mechanisms of the effects on healthy tissue and use this to reduce the damage to healthy tissue.
For our research, we mainly use mice and rats to study the effect of radiation on organs. You need an intact organism for this because radiation not only has local effects on the cells but also interacts with tissues and organs throughout the body, such as the immune system. However, there are certainly alternatives to unravel part of the mechanisms.
We are the first to create organoids from cells of salivary glands. Organoids are mini-organs formed from stem cells, in this case from the salivary glands of mice and humans. With these organoids, we can conduct radiation research. When irradiating tumors in the head and neck, the salivary glands are often affected, resulting in patients having a dry mouth, difficulty eating, loss of taste, difficulty speaking, a high risk of tooth decay, tooth loss, and mouth infections. This leads to dry mouth syndrome, also known as xerostomia. To restore these salivary glands, we try to inject healthy cells derived from organoids, cultured from tissue obtained from the patient themselves, after radiation. This is similar to a bone marrow transplant. After introducing these cells, the salivary glands began to recover.
We now use far fewer animals than before, mainly due to the use of organoids. Organoids help us answer research questions at the cell and organ level. The next step is always to see how this works in an organ in interaction with blood vessels and the immune system and ultimately with the whole body. For the animals we use, we try to make it as comfortable as possible because you never want to cause more harm to your animals than necessary to achieve good results that answer your specific question. A sick or unhappy animal shows all kinds of effects that have nothing to do with what you are researching, which can lead to incorrect conclusions, besides the fact that it is not pleasant to harm an animal.
In December 2022, based on such animal experiments, we treated a patient for the first time in the world in a phase I/II clinical study to test the feasibility and side effects of such a treatment.”