Utilising microbial effectors and precisionmedicine to overcome immunotherapy resistance in colorectal cancer

01/09/2026 to 31/08/2029

Basic research and clinical translation have tremendously improved our understanding and the treatment of cancer. Precision medicine approaches have further improved cancer therapy, including colorectal cancer. Generally speaking, precision medicine is arguably most advanced in oncology. Despite these fruitful efforts, precision medicine prolongs survival rather than inducing complete remission, particularly in late-stage metastatic cancers. Importantly, metastatic disease accounts for up to 90% of all cancer related deaths, which highlights the need for effective treatments for this disease stage. Immunotherapies such as checkpoint blockade-, chimeric antigen receptor T cell- or bispecific antibody therapies, have transformed cancer patient management as long-term, complete remissions are achievable through these treatments. Unfortunately, only a small fraction of patients responds well to immunotherapies across various cancers. This is also true for colon cancer where 85-90% of patients do not respond well to checkpoint blockade therapy. Therefore, precision medicine approaches to overcome primary or secondary resistance to immunotherapies are critically needed. The microbiome is now a well-accepted modulator of immunotherapy efficacy. Indeed, specific bacteria and particular products are known to improve immunotherapy efficacy and may overcome secondary resistance. In this project we will analyse if genetic and microenvironmental factors drive resitance and means to overcome this. the question which effector molecule(s) downstream of the driver mutation confers protection. Taken together this aims at guiding precision medicine approaches and elevate cancer therapy.