hard on the heart.
heart cells Gleevec-treated ( top ) may develop abnormalities not seen in untreated cells ( background ).
Risto Kerkelä
Gleevec, the first of a vaunted line targeted cancer drugs with minimal side effects, can cause heart failure, according to new study . Researchers agree that the benefits of Gleevec worth the risk to patients desperately ill leukemia, but the study may encourage doctors to closely monitor for cardiac side effects.
For decades, drugs against cancer caused nausea and other debilitating side effects because they attack healthy tissue and cancerous tissue. Then, in 01, Novartis issued Gleevec (imatinib mesylate). The drug blocks a mutant protein that causes chronic myeloid leukemia (CML), becoming the first chemotherapy to specifically target cancer cells. CML was uniformly lethal, but today more than 70% of Gleevec patients in remission.
Cardiologist Thomas Force of Thomas Jefferson University in Philadelphia, Pennsylvania, began to doubt the safety of Glivec in 04 after the cardiologist Jean-Bernard Durand of MD Anderson Cancer Center in Houston, Texas, told him about 10 patients on the drug whose heart was normally pumped before treatment Gleevec but who had developed advanced heart failure after an average of seven months on the drug.
to see if heart failure was due to Gleevec, Durand and colleagues first examined biopsies of patient's heart muscles; they found abnormalities in the cell membranes which are characteristic of cardiac damages induced by the toxin. The work team then showed that Gleevec caused mouse hearts and mouse heart cells in culture to develop similar anomalies.
How Gleevec hearts be hurt? The drug targeting a mutant protein in cancer cells called Bcr-Abl, abnormal fusion of two normal cellular proteins, and Bcr-Abl. The team suspects that Gleevec may damage heart cells by disrupting Abl, a protein that normally regulates the growth and helps cells respond to stress. So strength and his colleagues took muscle heart cells cultured mouse and gave Abl either normal or variant Abl that is impervious to Gleevec. Even with additional normal on hand Abl, heart cells became sick again when we added Gleevec. But these cells with Gleevec-resistant Abl were fine, suggesting that targeting Gleevec Abl in normal heart cells causes heart failure in patients on medication. Force warns that other drugs against cancer that target enzymes linked Abl can also damage the heart. The researchers reported their findings online today in Nature Medicine .
hematologist George Daley of Boston Children's Hospital said that "they have marshaled a number of different pieces of evidence to suggest that there is [heart cell] direct toxicity." Novartis said in a statement says that more than 0,000 patients on Gleevec were checked, as life benefits are worth the risks, and that the cardiac side effects are "extremely rare." But the strength and cardiologists colleagues plan to check for themselves. They are planning a registry of 0 patients in their clinics that will monitor closely the hearts of cancer patients on Gleevec
Related Sites
- Background Gleevec FDA
- More information about CML
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