More concern about Gleevec

            PHILADELPIA - 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, Newswise reported. Not only that, similarly based drugs - tyrosine kinase inhibitors - could lead to heart problems, too, say scientists at the Center for Translational Medicine at Jefferson Medical College. A team of scientists led by Dr. Thomas Force, the James C. Wilson Professor of Medicine at Jefferson Medical College of Thomas Jefferson University, has shown in mice and in heart cells in culture that Gleevec can cause heart failure. The study, prompted by 10 patients with chronic myelogenous leukemia (CML) who developed severe congestive heart failure taking Gleevec, was online at Nature Medicine. “We found 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. 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 into overdrive because of a chromosomal mix-up that occurs during blood cell development. The genes ABL and BCR become fused and produce a hybrid BCR - ABL enzyme that is always active. The overactive BCR - ABL , in turn, drives the excessive proliferation of white blood cells that is the hallmark of CML. According to Dr. Force, 10 patients taking Gleevec at the University of Texas ’ M.D. Anderson Cancer Center in Houston developed fairly severe heart failure, with no prior symptoms. Because physicians there took baseline measures of the patients left ventricular heart function, the team was able to determine heart failure developed in these patients between two and 14 months after beginning Gleevec.