For people with cancer, chemotherapy can prolong life. However, chemotherapy-induced heart failure is increasingly being recognized as a major clinical challenge. A team of scientists from Canada and France are investigating imatinibmesylate (imatinib), a highly selective and effective anticancer drug, to understand its effects on the heart. Their study, which was published in the European Journal of Heart Failure, reveals that imatinib is toxic to the heart and causes overt damage to older hearts.
Imatinib is used in the life-long treatment of many cancers, most notably chronic myelogenous leukemia (CML). Because clinical evidence of cardiac toxicity is often delayed, there have been conflicting reports about the effects of imatinib on the heart. However, a team of researchers led by Dr. Mona Nemer, Professor of Medicine and Vice-President, Research at the University of Ottawa, has now produced clinical evidence that imatinib targets heart muscle cells in particular and that aging sensitizes the heart to negative side effects.
Imatinib therapy is extremely effective at targeting cancer but, in the end, we want to make sure that the treatment prolongs life, said Dr. Mona Nemer. Our study points to the need for careful monitoring of heart function during and after chemotherapy.
The study also uncovered the cellular pathways that are negatively targeted by the drug, and it opens the way for the development of therapeutic agents to prevent heart failure.
Understanding how cancer treatment affects the heart and what factors put our patients at risk for heart failure is critical. A better understanding of what causes heart failure enables us to protect our patients so they can enjoy disease-free lives, said Dr. Peter Liu, cardiologist and Scientific Director at the University of Ottawa Heart Institute.
With the development of more effective anticancer drugs, it has become evident that damage to the heart may occur as a result of cancer treatment, said Dr. Susan Dent, medical oncologist at the Ottawa Hospital. This is why we established, in 2008, the cardiac oncology program to further research and education, and to improve clinical care of cancer patients. Identifying risk factors and early signs of cardiac damage is crucial to maintaining heart health in cancer patients.
Imatinib was the first of a new generation of highly selective anticancer drugs that have paved the way for several new therapies. Like all tyrosine-kinase inhibitors, imatinib works by inhibiting an enzyme needed for cancer to develop, thus preventing the growth of cancer cells. The researchers discovered that in the heart, the drug interferes with the function of GATA4, a protein that is essential for cardiac muscle survival, resulting in cell death and, ultimately, heart failure.
This scientific work is supported by grants from the Canadian Institutes of Health Research.
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