Metabolic alterations driving PDAC-associated muscle wasting

Cachexia is a devastating muscle and fat wasting syndrome that affects many individuals with chronic disease, especially cancer. Pancreatic cancer patients are particularly at risk, with up to 70-80 percent exhibiting significant muscle wasting. This is a troubling statistic given the tight correlation between muscle wasting and patient outcomes, including mortality, morbidity, response to chemotherapy, and surgical prognosis. Despite decades of extensive pre-clinical/clinical research, therapeutic options for cachexia are limited. Dr. Doles? team aims to understand how muscle repair and regeneration are impaired in pancreatic cancer-associated cachexia. This proposal focuses on metabolic regulation of skeletal muscle stem cells (satellite cells), and will dissect how pancreatic cancer-associated secreted factors disrupt satellite cell metabolism and muscle regeneration. Successful completion of these studies will pave the way for future work investigating metabolic interventions capable of stimulating satellite cell expansion, thus boosting the endogenous regenerative capacity of skeletal muscle in pancreatic cancer patients.