IDEAS grants are intended to support investigators in British Columbia, Canada interested in extending their research and expertise to pancreatic cancer and join a growing list of collaborating scientists and clinicians at Pancreas Centre BC, a multidisciplinary research centre dedicated to improving the outcomes of pancreatic cancer.
Andrew Minchinton
Exploiting hypoxia in pancreatic cancer: turning a liability into a therapeutic target
Hypoxic tumour cells are arguably the most widely validated targets in cancer, playing a significant role in pathogenesis and in resistance to radiotherapy as well as to systemic chemotherapies and immunotherapies. Pancreatic cancer has one of the most hypoxic microenvironments, and due to a very aggressive and treatment-resistant phenotype, has the greatest need for innovative and novel approaches to therapy, making it a highly suitable model for investigating novel hypoxia-targeted treatments. Attempts to eradicate the hypoxic pancreatic cancer cell population have previously been hindered by difficulty in measuring tumour hypoxia.
In collaboration with Dr. Reinsberg, we have developed an Oxygen Enhanced MRI (OE-MRI) biomarker of hypoxia in pancreatic cancer models. OE-MRI is a clinically translatable technique that measures differences in tumour oxygenation when patients breathe 100% oxygen. Our aim is to prospectively screen pancreatic tumour-bearing mice with OE-MRI ahead of hypoxia-sensitive treatments of radiation, hypoxic cytotoxin evofosfamide and hypoxia-activated DNA damage repair inhibitors to develop OE-MRI as a predictive biomarker of pancreatic tumour response to hypoxia-sensitive therapies. To achieve our aim, we will monitor the response to treatment of individual animals, and correlate treatment efficacy with pre-treatment hypoxia profiles in a panel of PDX PaCa models grown in mice.
This research will provide validation of OE-MRI as a predictive biomarker for hypoxia-targeted therapies in pancreatic cancer such that it can be recommended for future application in patients at the BC Cancer Agency in Vancouver where hypoxia-activated DNA damage repair inhibitors are in late-stage development in the Minchinton laboratory.
For more information about Andrew Minchinton and his research click here