Abstract
Despite screening campaigns, 8,000 people in Belgium are diagnosed with colorectal cancer annually. Of these, 25% of patients already have metastases at the time of diagnosis, and an additional 40% will develop metastases during their disease progression. The treatment of patients in an advanced stage mainly relies on multi-drug chemotherapies that can be combined with targeted therapies, but with limited success. This group of patients therefore needs new, improved treatments. In colorectal cancer, there is a close interaction between tumor cells and the tumor microenvironment, of which cancer-associated fibroblasts are the most common cells. These are also involved in the formation, growth, and migration of the tumor and can form a shield around the tumor that hinders the effect of systemic therapies. However, it has been found that not all cancer-associated fibroblasts contribute to tumor progression, and it is important to selectively target them. In our lab, we have discovered a subgroup of cancer-associated fibroblasts with a high expression of CD70 that are more common in advanced stages and are clearly associated with tumor migration and immune suppression. We are convinced that targeting these CD70+ cancer-associated fibroblasts can improve the efficacy of chemotherapy. In this project, I aim to investigate whether a CD70-targeted immune cell therapy can significantly improve the effect of first-line chemotherapies using state-of-the-art 3D culture models and an in-house developed drug screen imaging platform.
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