Grant: Master's Award: Canada Graduate Scholarships

The number of cancer survivors is growing worldwide, thanks to improved cancer diagnostics and treatments. However, neurological adverse effects are highly common in cancer treatments such as chemotherapy-induced cognitive impairment or chemobrain, which can last for years, seriously impacting treatment adherence and quality of life of cancer patients and survivors. Currently there is no treatment available for chemobrain. Thus, we aim to discover novel mechanisms and test a potential treatment for chemobrain. Methionine (Met) is an essential amino acid that can cause neurotoxicity when consumed in high quantities while limiting its intake is neuroprotective and improves cognitive health. Further, Met restriction can enhance response to anti-cancer treatment in mice, and may be ideal as an adjuvant treatment during chemotherapy. Therefore, we will test the hypothesis that chemobrain can be prevented by limiting dietary Met intake. To test this, mice are treated with 5-fluorouracil (5FU), a common chemotherapy drug used for many cancers, to investigate changes in the hippocampus, a critical brain region for memory function that is vulnerable to chemobrain. As 5FU and Met restriction may alter a broad range of cellular functions, we need a comprehensive strategy to understand their effects. Here, single-cell RNA sequencing will be performed on the hippocampus of mice treated with 5FU and/or low-Met diet. This research will identify gene biomarkers for chemobrain that can be used to further investigate the mechanisms and to test potential therapeutics. The results will help develop strategies to limit neurological side effects of cancer treatment, which is paramount to improve treatment adherence and the quality of life of cancer patients.