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"Miracle" Cancer Drug Gleevec Can be Toxic to the Heart

Gleevec, the wildly successful poster-child of a new generation of cancer drugs aimed at specific targets in the cancer cell, can be dangerous to the heart.// Not only that, but other similarly based drugs – called tyrosine kinase inhibitors – could lead to heart problems as well, say researchers at the Center for Translational Medicine at Jefferson Medical College in Philadelphia.

A team of scientists led by Thomas Force, M.D., James C. Wilson Professor of Medicine at Jefferson Medical College of Thomas Jefferson University, has shown in studies in both mice and in heart cells in culture that Gleevec can cause heart failure. The results of the study, prompted by 10 patients with chronic myelogenous leukemia (CML) who developed severe congestive heart failure while taking Gleevec, appear July 23, 2006, in an advanced online edition of the journal Nature Medicine.

“We found that the molecular target of the drug, the Abelson tyrosine kinase (ABL) protein, serves a maintenance function in cardiac muscle cells and is necessary for their health,” Dr. Force explains. “While the cancer is treated effectively, there will be some percentage of patients who could experience significant left ventricular dysfunction and even heart failure from this.”

“Gleevec is a wonderful drug and patients with these diseases need to be on it,” he says. “We’re trying to call attention to the fact that Gleevec and other similar drugs coming along could have significant side effects on the heart and clinicians need to be aware of this. It’s a potential problem because the number of targeted agents is growing rapidly.”

Gleevec is a new type of cancer drug – the first of its kind developed to fight cancer by turning off an enzyme that causes cells to become cancerous and multiply. In CML, an enzyme called ABL goes in overdrive because of a chromosomal mix-up that occurs during blood cell development. The genes ABL and BCR become fused and produce a
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