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Finding key to cancer drug Gleevec's limitations
Date:8/5/2009

ANN ARBOR, Mich. University of Michigan researchers have developed an animal model that provides strong evidence why imatinib, marketed as Gleevec, helps patients with chronic myeloid leukemia survive longer, but does not keep the disease from returning if treatment ends.

Leukemia-initiating cells are able to live below the drug's radar and enable the disease to recur in most cases after treatment stops, the researchers report in the August issue of Cancer Cell.

The researchers already are using their findings to test combinations of imatinib and other drugs to find ways to sensitize the leukemia-initiating cells to imatinib and enhance its power.

Context

Imatinib, now the standard first-line treatment for chronic myeloid leukemia or CML, has prolonged lives, but does not keep many patients from eventually moving into the disease's later, more severe stages.

Until imatinib was introduced in 2001, people with CML faced a grim prognosis, with few surviving five years after diagnosis unless they received bone marrow transplants. Imatinib has reversed that prospect, allowing 95 percent of people with CML to survive five years.

Yet it soon became clear that the disease almost always returns without maintenance treatments of imatinib. Imatinib treatment cures the disease in at best 5 percent of cases. Maintenance treatments are a concern, because the drug can cause side effects such as extreme fatigue, nausea, diarrhea and muscle pain. These force 15 percent of cancer patients to stop taking imatinib; some then undergo bone marrow transplants, the only treatment known to cure CML.

Imatinib, one of several targeted cancer therapies developed in recent years, inhibits certain enzymes associated with mutated genes that are involved in CML. Cancer researchers have suspected but have not known until now that certain cells that set events in motion toward CML are able to resist the dr
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Contact: Anne Rueter
arueter@umich.edu
734-764-2220
University of Michigan Health System
Source:Eurekalert  

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