Grant: CIHR Fellowship

Hypoxia, or low oxygen, occurs in tumours with disrupted blood vessels. Cancer cells in hypoxic tumours are resistant to both radiation and chemotherapy, and increase risk for cancer progression. To improve cancer therapy, it is therefore important to develop strategies that prevent blood vessel disruption in tumours and eliminate hypoxia. A group of drugs named "Angiotensin Receptor Blockers", or ARBs for short, are widely prescribed to treat high blood pressure. Interestingly, we found that that ARBs may be repurposed to prevent blood vessel disruption in tumours. This research project will investigate which cells in tumours are targeted by ARBs in order to identify which patients can benefit from ARBs, if there are any treatments that may act similar to ARBs but more effectively, and if the benefits of ARBs may be applied to other diseases. We are studying how ARBs affect cells called "fibroblasts". Fibroblasts respond to injuries by attempting to rebuild the basic structure of the body, such as creating a scar to heal a cut. Similarly, fibroblasts respond to a cancerous growth by modifying the structure of a tumour. We believe that fibroblasts are critical in causing disruption of tumour blood vessels, leading to hypoxia. We will apply techniques that assess how ARBs alter the DNA of fibroblasts, and whether the changes to fibroblast DNA affect tumour structure. These experiments will advance the fundamental understanding of fibroblast biology and determine how ARBs control tumour structure to alter the effectiveness of cancer therapy as well as other fibrotic conditions. As ARBs are already approved drugs and many cancer patients are already taking ARBs to treat high blood pressure, this research project will connect laboratory studies on fibroblasts with clinical data. Doing so will allow the findings from our proposed research to be applied towards improving clinical care relatively soon.