Grant: Canada Postdoctoral Research Award (CPRA) program

Solid tumours do not always develop enough blood vessels to bring oxygen to their cells, which can cause the tumour to form regions with low oxygen levels and high acidity. This type of environment has been associated with more aggressive cancers that are resistant to conventional treatment options. In cultured human cells, the same conditions have recently been shown to trigger the formation of protein deposits called amyloid bodies. These structures form inside the nucleus of the cell and prevent cells from dividing. Initial experiments have found that amyloid bodies can form inside the cells within tumour cores, where they supress tumour growth. Given that many common cancer treatments target only growing tumours, it is possible that amyloid body formation could prevent cells from being killed by these therapeutic approaches. Here, we plan to generate human tumours in a mouse model and assess the formation of amyloid bodies in regions with low oxygen levels. Once the tumour types that form amyloid bodies have been identified, we will suppress amyloid body formation in corresponding cancer cell lines grown in low-oxygen conditions, to see if it makes conventional cancer treatments more effective. We will also stain patient-derived tumour sections for amyloid body formation, to identify cancer types that may benefit from this treatment approach. This could lead to the development of new combination therapies to target treatment-resistant tumours, where amyloid body inhibitors are used together with conventional cancer treatments to sensitize the dormant cells to chemotherapy and radiation, allowing more tumour cells to be killed.