Jefferson scientists show 'miracle' cancer drug Gleevec can be toxic to...( e cancer cell targets at once to up the...),Health

In Gleevec, for example, blocking the PDGF receptor is crucial to its effect in thwarting gastrointestinal stromal tumors. Designing a drug to inhibit the PDGF receptor but not ABL, then, could still work against such tumors but not cause heart problems.

"We've learned something about the biology of the heart," Dr. Force says. "ABL is important for cardiomyocyte health. We also can learn something about how to stay away from these targets that are important and optimize the drugs."

In other studies, the researchers attempted to find the biological pathways involved in causing heart cells to die. They found that Gleevec appears to cause endoplasmic reticulum stress, which is initially a protective response by the cell, but if sustained, leads to cell death. They also found that treating mice heart cells with Gleevec led to the cells losing mitochondrial function, leading to cell death.

Jefferson, in collaboration with M.D. Anderson, the Cleveland Clinic and one or more European centers is planning to begin a registry for new tyrosine kinase inhibitors. "As these drugs come out, we can more easily collect data on larger numbers of patients as they take the drugs to get an idea of the incidence of heart problems," Dr. Force explains.

Dr. Force doesn't think it's possible to screen for potential heart problems that could be related to Gleevec. He notes that physicians involved in pre-release clinical trials of tyrosine kinase inhibitors will be aware of the potential problems and evaluate heart function if symptoms or signs possibly due to heart failure appear.

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Contact: Steve Benowitz
steven.benowitz@jefferson.edu
215-955-5291
Thomas Jefferson University
23-Jul-2006