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Novel combination overcomes drug-resistant myeloma cells

BOSTON--A novel strategy devised by Dana-Farber Cancer Institute scientists has proved highly effective in killing drug-resistant multiple myeloma cells in the laboratory and could open a new form of attack on the deadly blood cancer, they report.

Highly encouraged by the findings, the researchers hope to move rapidly to clinical trials of the therapy, a combination of the drug Velcade and an experimental compound that was designed by researchers at the Broad Institute of Massachusetts Institute of Technology and Harvard University.

The report, which will be posted online this week by the Proceedings of the National Academy of Sciences (http://www.pnas.org/papbyrecent.shtml), demonstrates that the combination was more than twice as effective as either drug alone in killing resistant cells from patients' bone marrow.

The promise is particularly exciting, scientists say, because many patients don't respond to Velcade, a drug approved just two years ago that's been an important new therapy for multiple myeloma, a disease which caused an estimated 11,000 deaths in 2004, according to the Multiple Myeloma Research Foundation.

"This is not just another drug, this is a whole new approach to treating multiple myeloma," said Kenneth Anderson, MD, senior author of the paper, whose lead author is Teru Hideshima, MD, also of Dana-Farber. Others include Stuart L. Schreiber, PhD, of Harvard University and the Broad Institute, and Jay Bradner, MD, of Dana-Farber and the Broad Institute.

Velcade is the first in a class of so-called proteasome inhibitors, which cause lethal stress in cancer cells by blocking the proteasome, a disposal mechanism that rids the cell of abnormal proteins. Cells in which the proteasome is jammed eventually commit suicide, triggered by the accumulation of proteins, explains Anderson, who is also the Kraft Family Professor of Medicine at Harvard Medical School.
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Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
2-Jun-2005


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