Stress-induced intracellular amyloid aggregation as a novel mechanism of therapeutic resistance

Many cancers can form tumours that do not receive enough oxygen. This can lead to regions with low oxygen levels, and high acidity. These same conditions can cause cells to form protein deposits called “amyloid bodies”. When amyloid bodies form, it prevents cells from dividing. Preliminary experiments have shown that amyloid bodies can form in some solid tumours and prevent growth. Since many chemotherapies only target growing tumours, it is possible that amyloid body formation allows cells to survive chemotherapy. In this project, we will grow cancer cells in low-oxygen conditions. Then, we will test the effects of chemotherapeutics in cells with and without amyloid bodies. Any cell types that are more sensitive to chemotherapy when amyloid bodies are inhibited will be used to generate tumours in mice. This will allow us to test this treatment in an animal model. We will also stain different tumour types to try to identify cancers that have high levels of amyloid body formation. This could lead to the development of new combination therapies to target treatment-resistant cells, by sensitizing dormant, non-dividing cells to chemotherapy.