Metabolic Modulation As A Novel Therapy For Chemotherapy-Induced Cardiotoxicity

Introduction: Chemotherapy Induced Cardiotoxicity (CIC) is a serious complication that results in early termination of cancer therapies, despite responsive tumours. There are no therapies that prevent CIC, as our understanding of the mechanisms in this condition is limited. Intriguingly, similar metabolic processes (increased glycolysis) has been described in heart failure and cancer, suggesting metabolic therapies may be beneficial against both diseases. One challenge in designing CIC therapies is protecting the heart against apoptosis without hindering chemotherapy-mediated tumour apoptosis. An intriguing difference between the myocardial and tumour microenvironments is the former is normoxic (oxidized) and the latter hypoxic (reduced), suggesting that targeting metabolic redox-sensitive proteins induced by chemotherapy agents in the heart may provide selectivity against CIC, without compromising tumour suppression. Hypothesis: We hypothesized that therapeutically targeting the metabolic redox-sensitive...