Colon cancer is a very common malignancy with a high burden of disease and mortality. Unfortunately, improvements in the outcome of disease have been limited in the last decades. A major contributing factor to this fact is that colon cancer is a highly heterogeneous disease. Both the variation in characteristics of colon cancers between individual patients is very large, and also within one colon tumor the cells can be widely distinct. These two aspects make it difficult to devise new therapies that effectively target all tumors, and all cells within the cancers. Therefore, personalized strategies are required to classify patients in subgroups with similar characteristics, and that in the future might guide treatment decisions. In addition, the variation in cell types within individual cancers needs to be understood better to make sure that we can effectively kill as many tumor cells as possible and not only specific populations.
The questions raised above are of major importance for society as annually 1.2 million cases of colorectal cancer are seen worldwide, and approximately 50% of these patients die as a result of this disease. Clearly, developments of novel more effective treatment strategies are therefore required. In order to achieve this more, fundamental insights in the biology of colon cancers and the origins of heterogeneity are pivotal.
The project CRCStemCellDynamics aims to understand how stem cells contribute to the heterogeneity of colon cancers both between patients and within individual cancers. We investigate how the specific cell of origin impacts on the properties of the resulting cancer. In addition we study how stem cell-like cells within established colon cancer tissue are responsible for the observation that within individual cancers some cells do respond to therapy and other do not, allowing for relapse of the disease. We study this by using state of the art biomolecular cancer models in combination with bioinformatic- and mathematical analyses.