The powerful drugs used to kill cancer cells also harm normal cells, a negative but unavoidable impact of these therapies. A researcher at the Royal College of Surgeons in Ireland is looking at how the heart is affected by such drugs in the hope of finding a way to protect these critical tissues.
Dr Noreen Dowd, an RCSI lecturer in anaesthesia based at Beaumont Hospital, is looking in particular at an enzyme that is released when damage is caused. This enzyme in turn causes the body to produce a group of proteins, prostaglandins, some of which help protect the heart muscle.
"It appears that this is a protective response," Dr Dowd explained. "The potential benefit is if we can identify the protective prostaglandins we can administer them to a patient receiving these anti-cancer drugs." The key to the work is the initial enzyme, cyclooxygenase or COX for short. "Cyclooxygenase is an enzyme that is responsible for the production of prostaglandins," Dr Dowd explained. They have a wide range of activities in the body, for example in blood clotting, protection of the stomach lining and in kidney function.
International research has revealed there were two isolates of this enzyme, COX1 and COX2. COX1 was produced under normal conditions but COX2 would arise in response to an inflammatory situation. Other research had shown that COX2 also seemed to have this protective aspect in relation to heart tissue. While this protective potential had been shown in vitro, she wanted to test it in vivo using rats.
One anti-cancer drug in particular, doxorubicin, was very effective against cancer cells but also causes damage to the heart. Dr Dowd and her research colleague, Ms Sharon Adderley, with Prof Anthony Cunningham and Prof Des Fitzgerald, began studying the biochemical connections between COX2, prostaglandin and heart tissues.
The anti-cancer drug produces free radicals, compounds which contain highly reactive oxygen. These in turn can react with healthy cells and cancer cells, causing damage to critical cell elements including DNA.
"We are trying to bridge the gap between in vitro and in vivo" understanding of the prostaglandins' benefit, she said. They looked at the detailed biochemistry, cell morphology and function as these biochemical reactions took place. They found there was some incomplete protection given by the production of COX2 and its related prostaglandins.
The challenge now, she said, was to isolate those prostaglandins which have a beneficial effect on heart muscle. These could then be given to patients receiving doxorubicin so its advantages in killing cancer cells can be fully harnessed and its side effects reduced.
Dr Dowd's work was a good example of how researchers at the Royal College of Surgeons in Ireland were trying to discover new approaches to clinical medicine, explained Prof Des Fitzgerald, head of the Department of Clinical Pharmacology at the RCSI. The research attempts to understand how drugs work inside the body. "It is a strategy we have pursued here, trying to combine clinical and basic research," he said.