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Approved Lymphoma Drug Shows Promise in Early Tests Against Bone Cancer
Date:11/5/2009

Runx2 both blocks the growth of bone cancer cells and triggers a quality control mechanism that causes abnormal cells to self-destruct. For some reason, however, Runx2 levels are dramatically reduced in bone cancer cells.

In the current study, researchers found that Bortezomib shuts down cellular machines that destroy Runx2, machines that become overactive in bone cancer patients. Bortezomib restored Runx2 levels in osteosarcoma cell lines and in osteosarcoma tumors in mice. In addition, tests found a three-fold increase in the bortezomib-treated group in the number of cancer cells testing positive for an enzyme (caspase-3) known to drive them to self-destruct. Experiments also showed that the average size of osteosarcoma tumors in bortezomib-treated mice was only 30 percent of that in the control group.

The new findings also provide the first explanation of why Runx2 levels are lower in bone cancer cells. Researchers found that Runx2, which encourages abnormal cells to self destruct, may itself become the target of cellular machines called proteosomes that break down and recycle unneeded proteins.

Specifically, the team found in osteosarcoma cells high levels of a protein called Smurf1, known to tag aging proteins for attention by protein-devouring proteosomes. The team is now looking at why levels of Smurf1 are higher in osteosarcoma. In addition, Eliseev and colleagues plan to launch a pilot study later in 2010 using bortezomib to treat osteosarcoma.

Along with Eliseev, the work was led by Yuriy Shapovalov, David Benavidez and Daniel Zuch within the Center for Musculoskeletal Research at the Medical Center. The study was funded in part by the Karen D'Amico Foundation, the James P. Wilmot Foundation and the National Institutes of Health.

"These data argue that bortezomib treatment not only caused bone cancer cells to signal fo
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SOURCE University of Rochester Medical Center
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