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Archive - May 7, 2013

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Researchers Describe a Way That Breast Cancer Cells Acquire Drug Resistance

A seven-year quest to understand how breast cancer cells resist treatment with the targeted therapy lapatinib has revealed a previously unknown molecular network that regulates cell death. The discovery provides new avenues to overcome drug resistance, according to researchers at Duke Cancer Institute. "We've revealed multiple new signaling pathways that regulate cell death," said Sally Kornbluth, Ph.D., vice dean of Basic Science and professor of Pharmacology and Cancer Biology at the Duke University School of Medicine. "And we've shown, at least in one disease, these signaling pathways can go awry in drug resistance. It also suggests you could manipulate these other pathways to overcome drug resistance." The researchers -- co-directed by Dr. Kornbluth and Neil Spector, M.D., associate professor of medicine at Duke -- identified a protein that effectively shuts down the signals that tell a cell to die, enabling cancer cells to keep growing. That protein, MDM2 (image), is already generating intense interest in the cancer research community because it is a master regulator of the tumor suppressor protein called p53. The new findings are published online on May 7, 2013 in Science Signaling. The Duke research team, with assistance from collaborators at the University of Michigan, identified a new role for MDM2 in activating cell death pathways independent of its role in regulating p53, a known initiator of cell death. More than half of all human tumors contain a mutation or deletion of the gene that controls p53. The researchers began by studying four different types of breast cancer cells that were able to keep growing despite treatment with lapatinib, a powerful drug that targets two growth pathways commonly disrupted in breast cancer, HER2 and epidermal growth factor receptor.

Advance in Understanding of Restless Legs Syndrome

Johns Hopkins researchers believe they may have discovered an explanation for the sleepless nights associated with restless legs syndrome (RLS), a symptom that persists even when the disruptive, overwhelming nocturnal urge to move the legs is treated successfully with medication. Neurologists have long believed RLS is related to a dysfunction in the way the brain uses the neurotransmitter dopamine, a chemical used by brain cells to communicate and produce smooth, purposeful muscle activity and movement. Disruption of these neurochemical signals, characteristic of Parkinson's disease, frequently results in involuntary movements. Drugs that increase dopamine levels are mainstay treatments for RLS, but studies have shown they don't significantly improve sleep. An estimated 5 percent of the U.S. population has RLS. The small new study, headed by Richard P. Allen, Ph.D., an associate professor of neurology at the Johns Hopkins University School of Medicine, used MRI to image the brain and found glutamate — a neurotransmitter involved in arousal — in abnormally high levels in people with RLS. The more glutamate the researchers found in the brains of those with RLS, the worse their sleep. The findings were published in the May 2013 issue of Neurology. "We may have solved the mystery of why getting rid of patients' urge to move their legs doesn't improve their sleep," Dr. Allen says. "We may have been looking at the wrong thing all along, or we may find that both dopamine and glutamate pathways play a role in RLS." For the study, Dr. Allen and his colleagues examined MRI images and recorded glutamate activity in the thalamus, the part of the brain involved with the regulation of consciousness, sleep, and alertness. They looked at images of 28 people with RLS and 20 people without.