Dutch Cancer Society grants for Geert Kops and Ina Sonnen

Kops: The role of chromosomal abnormalities in the development of colorectal cancer

The group of Geert Kops will use the grant to investigate the role of large-scale chromosomal changes in the development of colorectal cancer. Thomas van Ravesteyn, researcher in the Kops group, explains: “In more than 90% of the tumors there is an increase or decrease in the number of chromosomes in the cells. The precise changes are quite specific for each type of tumor. Therefore, it is likely that these chromosomal abnormalities play an important role in the development of the tumors. In colorectal cancer, which is our topic of interest, we also see such changes, but we do not yet know exactly how these chromosomal abnormalities arise and what the exact effect is on the cells. If we understand that better, we can also better understand the development of colorectal cancer.”

Colorectal cancer usually develops from a benign polyp. Because approximately 5% of colon polyps develop into colorectal cancer, larger polyps are detected through population screening and removed as a precaution. Pieces of tissue from these removed polyps form the basis for this research project by the Kops group. Van Ravesteyn: “We are working on this together with Beatriz Carvalho (research group Gerrit Meijer) from the Netherlands Cancer Institute, who has made organoids from removed colon polyps from patients. With these cultured mini-polyps we can study chromosomal abnormalities in the lab. We are going to monitor the organoids over time to see exactly when the abnormalities arise, and, for example, whether they arise at the same time or accumulate over time. Once we have a clear picture of this, we also want to know what exactly goes wrong during cell division that causes chromosomal abnormalities and how these aberrations cause a polyp to develop malignant properties. With this knowledge we can hopefully better predict which polyps can develop into colorectal cancer. This could contribute to new methods for detecting and treating colorectal cancer in an early stage. Thanks to the grant from the Dutch Cancer Society, we can now really start investigating this systematically.”

Sonnen: The role is signaling dynamics in colorectal cancer

The group of Ina Sonnen will use the funding from the Dutch Cancer Society to study the dynamics of signaling in colorectal cancer. Sonnen: “Our group is interested in how cells communicate with each other through signals. We know from healthy cells that these signals are not constantly active, but change over time. These so-called dynamics are important for the message that the signals convey.” Despite the importance of these dynamics, little is known about changes in these dynamics in tumors and their influence on the behavior of cancer cells. “In this research we will use organoids, mini-organs grown in the lab, to find out more about this. The advantage of these organoids is that we can look at the effect of mutations in tumors on signaling dynamics in a controlled system,” continues Sonnen. To transfer their findings to primary human patient samples, they will collaborate with the group of Hans Clevers.

Studying signaling dynamics in cells is complex, because signals in our cells are influenced by many other factors that either amplify or attenuate them through feedback. In order to get a clear picture of this complex system, the researchers will collaborate with the group of Federica Eduati (TU Eindhoven) for this project. They will translate the results from the lab into mathematical models and use these to predict optimized treatment regimes. Ultimately, the new insights obtained from these models can hopefully be used to optimize cancer therapies. “Current therapies have the disadvantage that they have many side effects for the patient. By learning more about the dynamics of signals and acting on them, we hope to be able to reduce these side effects and target tumor cells more efficiently in the future.”

Dutch Cancer Society

The Dutch Cancer Society is investing a total of 14.7 million euros in 23 new studies that focus on fundamental questions in the field of cancer. Five of these studies have been selected from the proceeds of Alpe d’HuZes. The aim of these studies is to discover how cancer cells work, what their limited places are and how we can switch to contain cancer. The full financing decision can be found on the website of the Dutch Cancer Society (only in Dutch).