Determining the heart safety of a new cancer drug

Raf kinases and cardiac ECs: Characterising Raf inhibition in chronic hypertension (Miss Susanna Cooper)

Research suggests that a class of cancer medicines called Raf inhibitors can affect cell-protective mechanisms in the heart. This project will determine whether these drugs could have a detrimental effect in people with heart and circulatory diseases. Raf is thought to be involved in regulating the tiny blood vessels in the heart called capillaries. This extensive network of capillaries is essential for supplying blood to the heart. In people with high blood pressure, the number of heart capillaries is reduced and cells that line the blood vessels (endothelial cells) begin to work less efficiently. Loss of capillaries and endothelial cells may be the underlying problem in some forms of heart failure, leading to heart muscle cell loss and increased formation of scar tissue. This project will determine if a new Raf-blocking drug accelerates this loss by studying its effect on human endothelial cells. A subset of the cells will be treated with angiotensin to simulate high blood pressure. They will also observe how the drug affects endothelial cells and heart capillaries in mice with high blood pressure. The results will reveal whether it is safe for people with high blood pressure or with conditions such as angina to be treated with this class of cancer drugs.