Manipulation of anti-lymphoma drug action by fatty acids

Omega-3 fatty acids, such as those contained in fish oil supplements, are considered to be beneficial to health and are often taken as a dietary supplement. Studies suggest that they can alleviate the side effects of chemotherapy, such as inflammation or unwanted weight loss. However, it is less clear whether omega-3 fatty acids also influence the effectiveness of chemotherapeutics. The current state of research is inconsistent, partly because the effects depend strongly on the chemical form of the fatty acids (free or bound in lipids) and the biological context. This project investigates the influence of different forms of omega-3 fatty acids on the treatment of Burkitt`s lymphoma, a particularly aggressive form of cancer. The starting point is data from animal experiments in which the administration of phospholipid- bound omega-3 fatty acids reduced the efficacy of a standard chemotherapeutic agent. At the same time, changes in cell metabolism, survival mechanisms and stress responses were observed. The aim is to systematically elucidate the underlying molecular mechanisms. To this end, comprehensive multiomics analyses are used to record changes at gene, protein and lipid level. The experiments are carried out on Myc-dependent lymphoma cells (or their precursors) in cell culture and in an immunocompetent mouse model, both under treatment with an anti- cancer agent. Early tumor development (e.g. in the blood and spleen) as well as the progression of existing tumors will be analyzed. In addition, survival data, immune cell populations and cancer-typical signaling pathways are recorded. Genetic and pharmacological interventions will clarify the functional relevance of the identified target structures. The project provides important insights into the risk-benefit assessment of omega-3 fatty acid supplementation during cancer therapy. It contributes to enabling more precise recommendations for clinical application in the context of chemotherapy - differentiated according to tumor prevention and therapy.