Can a targeted cancer drug help treat diabetes? That's a question two independent teams are asking after giving leukemia patients the drug Gleevec and watching their pre-existing diabetes regress. One 70-year-old woman improved so dramatically that she could no longer be classified as a type 2 diabetic, three physicians reported last week in the New England Journal of Medicine (NEJM).
Gleevec was designed to disable a defect in a protein called a tyrosine kinase that occurs in chronic myelogenous leukemia (CML), a blood cancer. The connection with diabetes doesn't come as a total surprise; Gleevec affects other protein kinases that indirectly help control insulin signaling and the body's response to insulin secreted by the pancreas. And it hits a protein kinase called platelet-derived growth factor, which may spur conditions, such as atherosclerosis, that are common complications of diabetes. Two recent mouse studies by Mark Cooper and colleagues at the Baker Heart Research Institute in Melbourne, Australia, showed that Gleevec helped animals with diabetes-induced atherosclerosis and diabetes-induced kidney disease.
The benefits may apply to humans, too. In the November 2004 Journal of Clinical Oncology, doctors at the University of Rome described seven patients with type 2 diabetes and CML. Six improved enough to reduce diabetes medications or insulin dosages. The only patient whose diabetes didn't ease, the team says, was also the only one whose leukemia didn't respond to Gleevec.
And now, in NEJM, Enzo Bonora, an endocrinologist at the University of Verona, and two hematologist colleagues report improvements in three more cancer patients with diabetes, including the elderly women. The Italians can't say whether an effect on insulin signaling is behind the unusual observations. Moreover, the cohort is tiny, Bonora stresses, so the findings should be viewed cautiously. "We don't know exactly what's going on," he says.
Neither do others. Brian Druker of Oregon Health & Science University in Portland, a hematologist-oncologist who helped develop Gleevec, says three or four diabetics with CML have been treated in his center, and he doesn't recall any change in their diabetes while on the drug. Yet Druker says the new findings are "hard to ignore."
Bonora plans to ask Novartis, the Swiss company that manufacturers Gleevec, to consider testing its drug in type 2 diabetes patients. Currently, Novartis is "not planning" any studies of Gleevec in type 2 diabetes, Novartis spokeswoman Kim Fox wrote in an email.