Research links protein regulation pathway to poor prognosis in breast cancer
Illustration: David Aten, Medical Graphics and Photography
How Gleevec® blocks morphine tolerance:
Opioid drugs, such as morphine, bind to the mu opioid receptor (MOR) on the surface of nerve cells. This process stimulates the release of platelet-derived growth factors (PDGF-AB and BB) from the cell. These growth factors then bind to the beta-isoform of the platelet-derived growth factor receptor (PDGFR-b). Activating this receptor causes tolerance to develop. Gleevec® (imatinib) blocks activation of the PDGFR-b. This stops tolerance from occurring and reverses pre-existing tolerance.
Commonly used drug eliminates morphine tolerance
Seeing children endure chronic pain associated with cancer treatment inspired Howard Gutstein, M.D., professor in MD Anderson’s Department of Anesthesiology and Perioperative Medicine and Department of Biochemistry and Molecular Biology, to focus his research on pain management.
Specifically, he wanted to find the cause of morphine tolerance, which develops over time and makes the drug ineffective for pain relief.
“If I could understand what causes morphine tolerance, I’d finally be able to treat these patients’ pain effectively and alleviate their suffering,” Gutstein says. He discovered the key to understanding morphine tolerance might be a cancer drug already in clinical use.
Gutstein and his colleagues found that the cellular process that causes morphine tolerance can be blocked by a reformulated form of imatinib, a drug commonly used to treat certain kinds of leukemia and gastrointestinal tumors.
Since imatinib, known by the brand name Gleevec®, is already approved for use in humans, Gutstein hopes soon to translate his findings on the reformulation of the drug through animal studies and Phase I trials in humans.
“We may be able to quickly translate this discovery and dramatically reduce the suffering endured by the sickest patients, and not just those with cancer,” Gutstein says.
Blocking tolerance would make lower doses of morphine more effective, also reducing undesirable side effects associated with it, including itchiness, nausea and difficulty breathing.
Reported in the February 2012 edition of Nature Medicine.
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