Unraveling Chemotherapy Resistance: Linking Tumor Metabolism, Cachexia, and Organoid Innovation

Therapy resistance remains a formidable challenge in both pancreatic and ovarian cancer. While many ovarian cancer patients initially respond well to platinum/paclitaxel chemotherapy, most eventually experience relapse and develop resistance to treatment. The underlying causes of this resistance are complex and not yet fully understood, with tumor genetics, metabolism, and body composition all playing crucial roles. Patients with cachexia show reduced responses to chemotherapy, limiting survival and impacting quality of life.

Tumor Metabolism and Cachexia

High tumor metabolic activity (characterized by increased glucose uptake and aerobic glycolysis) is a well-known contributor to chemotherapy resistance. Our pilot studies reveal that myosteatosis (fat accumulation within skeletal muscle), a hallmark of cancer cachexia, is associated with higher tumor metabolic activity. This finding suggests a direct link between cachexia-related body composition changes and reduced chemotherapy effectiveness. Therefore, we will enhance our organoid-based models of chemotherapy resistance by integrating cachexia-related data. This innovative approach allows us to more accurately mimic the tumor microenvironment and metabolic conditions seen in patients, providing deeper insights into the mechanisms of therapy resistance. This has the potential to provide valuable insights for developing more targeted and potentially new therapies by bridging the gap between tumor biology, metabolism, and patient body composition and may pave the way for more precise and effective cancer treatments.