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U-M researcher receives grant to develop new approaches to treat Ewing's sarcoma

Date Visible: 
02/06/2012 - 3:00pm
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Understanding how cancer cells survive is a primary focus of investigation in Elizabeth R. Lawlor's research

Ann Arbor - University of Michigan pediatric oncology researcher Elizabeth R. Lawlor, M.D., Ph.D., has received a $150,000, two-year grant from CureSearch for Children's Cancer to help study metabolic changes in Ewing sarcoma with the goal of developing new treatments for this bone cancer.

Understanding how these cancer cells survive is a primary focus of investigation in many research laboratories around the world, including Lawlor's. Lawlor is the Russell G. Adderley Professor of Pediatric Oncology and an associate professor of pediatrics and pathology at the U-M Medical School.

Ewing sarcoma is the second most common type of bone tumor in children and adolescents, typically affecting the pelvis, tibia, fibula, and femur. This cancer most often occurs in adolescents, with nearly half of cases arising when the patient is between the ages of 10 and 20.

While most patients with Ewing sarcoma respond to treatment, nearly a third with localized disease and almost all patients with metastases relapse after their initial remission. Although the reasons for relapse are complex and not yet completely understood, it is believed that in at least some cases, there are cells in the original tumor that survive despite highly toxic doses of chemotherapy.

Lawlor's lab previously identified that Ewing sarcoma cells have an abnormal response to stressful environments. Specifically, unlike normal cells, Ewing sarcoma cells survive when deprived of oxygen.

In collaboration with her colleague, Jeff Martens, Ph.D., an associate professor in the U-M Department of Pharmacology, Lawlor's group has discovered that suppression of the potassium ion channel Kv1.5 is, at least in part, responsible for this abnormal cell survival. Kv1.5 is a type of protein in cells that moves potassium out of cells. Lawlor hypothesizes that restoring expression of the Kv1.5 channel in Ewing sarcoma cells may inhibit their resistance to cell death and lead to better outcomes for patients.

To conduct this study, Lawlor and her team will study both normal and cancer cells to understand the mechanisms of Kv1.5 channel suppression in Ewing sarcoma.

"Cell death under conditions of stress requires that potassium ions move out of the cell," Lawlor says. "In cancer this is often blocked, leading to abnormal cell survival. If we can understand how this response is disrupted in Ewing sarcoma, we can develop tools to reactivate it. Ultimately, our goal is to use this knowledge to prevent survival of the most therapy-resistant cells and thereby prevent tumor relapse."

Lawlor's research is funded through the Nick Currey Fund at CureSearch for Children's Cancer. Established by Ralph and Nancy Currey in memory of their son, Nick, who died in November 2005 after a 14-month battle with cancer, the Nick Currey Fund's purpose is to support research to find a cure for the disease that took Nick's life - Ewing sarcoma. The Currey family hopes that research supported by the Nick Currey Fund will hasten the arrival of the day when no young person's life ends prematurely because of Ewing sarcoma.

The University of Michigan C.S. Mott Children's Hospital is consistently ranked as one of the best hospitals in the country. It was nationally ranked in all ten pediatric specialties in the U.S. News Media Group"s 2011 edition of "America's Best Children's Hospitals" including third in the country for heart and heart surgery. The hospital is now in a new 1.1 million square feet, $754 million state-of-the-art facility that is home to cutting-edge specialty services for newborns, children and women.

CureSearch for Children's Cancer is a national non-profit foundation whose mission is to fund and support children's cancer research and provide information and resources to all those affected by children's cancer. CureSearch raises funds for promising research conducted at more than 175 hospitals in the United States, participating in National Cancer Institute sponsored clinical trials conducted by the Children's Oncology Group. CureSearch also funds other clinical, basic and translational research so that researchers can understand all aspects of children's cancer, from its causes to its consequences.


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