DaCosta Lab Contributes to Canadian Pancreatic Cancer Research Strategy Workshop Report

150 150 DaCosta Lab

Summary of Scientific Presentation:

Ralph da Costa, “Investigating Radiation Response of Pancreatic Tumors, Their Vasculature and Microenvironment Using in Vivo Imaging to Identify New Treatment Strategies”
While stereotactic body radiotherapy (SBRT) shows promise for local control SBRT-induced vascular dysfunction, hypoxia are barriers. Candidate hypoxia-activated prodrugs (AQ4N) show potential, but require optimization. Newly discovered oxygen-generating nanoparticles (OGNPs) could be a clinical ‘game changer’ if tumor re-oxygenation with OGNPs enhanced AQ4N tumor cell cytotoxicity. To explore this potential, a novel preclinical optically-based imaging platform was developed that combines experimental microirradiation and advanced intravital imaging. The platform will be used to also investigate (at the cellular level and in living research animals bearing pancreatic tumors) the effects of tumor cell heterogeneity, tumor cell cycle dynamics, tumor vasculature and the microenvironment have on treatment.
Initial results are promising. SBRT (1×24 Gy) significantly increases hypoxia is BxPC3 pancreatic tumours grown in animals. Data from a pilot study measured survival in mice receiving OGNPs prior to irradiation compared with controls and found improved survival in the group receiving OGNPs, thereby suggesting that OGNPs may help enhance the tumor-killing effects of radiation therapy. Further study will explore whether AQ4N delivery can be timed to maximize tumor cell localization of the agent when radiation-induced tumor hypoxia is highest and whether OGNP can activate AQ4N once localized to hypoxic tumour cells by inducing tumor cells to enter the cell cycle, when AQ4N is most potent. If successful, these on-going early-stage preclinical studies may help to overcome a major treatment challenge in pancreatic cancer and possibly have clinical applications in other solid tumors treated by SBRT.