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UAMS, NCI discovery could advance multiple myeloma treatment 

UAMS news release

Cancer researchers at the University of Arkansas for Medical Sciences (UAMS) joined colleagues in a National Cancer Institute (NCI) study identifying changes in multiple myeloma cells that may offer a path for neutralizing malignant cells.

Researchers from the Myeloma Institute of Research and Therapy (MIRT) in the UAMS Arkansas Cancer Research Center (ACRC) were part of a team that found molecular mutations in multiple myeloma cells that activate an important biological pathway associated with cell growth and survival. This knowledge offers potential for new treatments for multiple myeloma, a cancer of the blood's plasma. Multiple myeloma is expected to result in 10,790 deaths and 19,900 newly diagnosed cases this year in the United States.

UAMS treats more than 2,250 patients with myeloma annually at the MIRT – more myeloma patients than are treated at any other facility in the country.

The results of this research appear in the August 2007 issue of the journal Cancer Cell. The study was a collaborative effort among basic scientists, pharmaceutical partners and UAMS' large clinical trial group.

“This is one of the largest collaborative translational cancer research efforts of its kind,” said John Shaughnessy, Jr., Ph.D., director of the Donna D. and Donald M. Lambert Laboratory of Myeloma Genetics and chief of Basic Sciences at the MIRT, and one of the study's authors.

“These results attest to the power of patient participation in clinical trials and the collaborative interactions between clinical and basic scientists. This research approach is anticipated to provide a quantum leap in the speed at which we understand how cancer starts, how best to treat it, how to prevent resistance to treatment and how to prevent the unwanted side effects associated with many treatment strategies currently in use.”

The research team's discovery began with the observation that a signaling pathway, called the NF-kappaB pathway, was activated in a majority of the multiple myeloma cells they tested. Using a novel drug that inhibits this pathway, researchers demonstrated that many myeloma cells either died or stopped dividing when the NF-kappaB pathway was disrupted.

The researchers were then able to show that the NF-kappaB pathway is activated in most of 451 primary tumor samples from patients with newly diagnosed multiple myeloma. This pathway is controlled at many levels and the researchers could identify mutations in at least one of the genes controlling NK-kappaB in 20 percent of the tumors.

“This work provides compelling genetic evidence for the involvement of the NF-kappaB pathway in multiple myeloma. This signaling pathway prevents cell death and therefore this study suggests inhibitors of the NF-kappaB pathway would provide a rational approach to the treatment of this cancer. This is an important prospect because currently our therapies are not aimed at genetically-defined pathways, and multiple myeloma remains difficult to treat,” said NCI Director John E. Niederhuber, M.D.

UAMS researchers made up nearly half of the 22 study authors. The MIRT conducted clinical work, tissue archiving and gene profiling for the study.

UAMS researchers involved in the study included Bart Barlogie, M.D., Ph.D., director of the MIRT and a professor of medicine and pathology; William T. Bellamy, Ph.D., associate professor of pathology; Madhumita Santra Ph.D., post-doctoral fellow in the Department of Pathology; Fenghuang Zhan M.D., Ph.D., assistant professor of medicine, Inchiro Hanamura, M.D., Ph.D., post-doctoral fellow in MIRT, and MIRT research associates Owen Stephens and David R. Williams.

The NCI is one of the National Institutes of Health. The UAMS research was supported by a grant from the NCI

UAMS is the state's only comprehensive academic health center, with five colleges, a graduate school, a medical center, six centers of excellence and a statewide network of regional centers. UAMS has about 2,435 students and 715 medical residents. It is one of the state's largest public employers with about 9,400 employees, including nearly 1,000 physicians who provide medical care to patients at UAMS, Arkansas Children's Hospital, the VA Medical Center and UAMS' Area Health Education Centers throughout the state. UAMS and its affiliates have an economic impact in Arkansas of $5 billion a year. For more information, visit www.uams.edu.

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