Grant: Operating Grant - PA: Cancer Research (bridge funding)

All solid tumours need a network of blood vessels that continuously expands to supply growing cancer cells with food and oxygen. Thus, drugs which stop the biological process responsible for creating new blood vessels were developed in the hopes of starving tumours by reducing their ability to grow new vasculature. Such drugs, when used in combination with regular chemotherapy, showed early promise in treating pancreatic cancer, but ultimately did not improve survival over regular chemotherapy alone. The first series of such drugs only attacks one major part, called the VEGF pathway, of the biological process, and oncologists now believe that other parts of the process must also be attacked. Thus, in Aim 1 of the proposal, pancreatic tumours, that are surgically removed from patients and then grown in the pancreas of mice, will be treated with a drug that interferes with multiple blood vessel-forming pathways including the VEGF pathway (sunitinib), and one that attacks multiple blood vessel-forming pathways but not the VEGF pathway (masitinib). Imaging technologies and biological methods will then be used to measure treatment-induced changes in tumour vessel formation, blood flow, and metabolic state before and during the course of treatment. The data will help us understand how these drugs work, and when changes to the blood vessels occur. In Aim 2, we will use the information from Aim 1 to plan treatments that combine either sunitinib or masitinib with standard chemotherapy that best exploits the physiological changes in the tumour in order to fully maximize the effects of such combination therapy. The efficacy of the chosen combination treatment regimen will be evaluated against standard chemotherapy. Findings from our work have the potential to guide the design of future clinical trials and improve present-day treatment outcomes of pancreatic cancer patients.