Grant: CIHR Fellowship

Pancreatic cancer (PDAC) is one of the most frequent causes of cancer death in Canada. The high mortality rate in PDAC results from disease detection at late stages, chemotherapy and radiation resistance and high incidence of recurrence. This may be due to the concomitant development of a dense stroma, a functionally supportive collection of cells, proteins and extracellular matrix; the stroma may act as a physical barrier preventing drug delivery and promote tumour growth, but also may protect the host from PDAC growth beyond the pancreas. Thus, understanding the interaction between the stroma and cancer cells is critical. Here we are proposing a systems-based approach to dissect the relationship between metabolism in tumour versus stroma in intact living PDAC models to identify mechanisms that regulate PDAC growth and understand the influence of short term fasting. Normal cells have developed strategies to adapt to fasting, however, little is known as to how cancer cells respond to the same stress and the effects on signaling networks and metabolism. By exploiting this difference in response to fasting, we may be placing a patient in a stress-resistant state where normal, healthy cells have a greater tolerance of therapies. By developing relevant cancer models that can be studied for long periods of time using imaging techniques that can follow tumour biology, these studies are expected to contribute important new information about PDAC development, leading to a future therapeutic intervention that is readily implemented (fasting) and could help reduce pancreatic cancer mortality and potentially completely eradicate pancreatic cancer outgrowth.