Approved Lymphoma Drug Shows Promise in Early Tests Against Bone Cancer
ROCHESTER, N.Y., Nov. 5 /PRNewswire-USNewswire/ -- A drug
already approved for the treatment of lymphoma may also slow the
growth of the most deadly bone cancer in children and teens,
according to an early-stage study published online today in the
International Journal of Cancer. The study drug, Bortezomib, was
found to be effective against bone cancer in human cancer cell
studies and in mice. While key experiments were in animals, the
cancer studied closely resembled the human form and the drug has
already been proven to be safe in human patients.
In the current study, researchers sought to use Bortezomib
(Velcade(R)) against osteosarcoma, an aggressive cancer that starts
in bone, spreads quickly and responds poorly to current
chemotherapies. The drug, a proteasome inhibitor developed by
Millennium Pharmaceuticals and Johnson & Johnson, was approved
by the FDA for the treatment of a rare, aggressive form of
non-Hodgkin's lymphoma in 2006 and for multiple myeloma in
"Our most clinically relevant finding is that a drug already
proven safe and effective in treating the most common cancers of
the blood may be equally effective in suppressing bone cancer,"
said Roman Eliseev, M.D., Ph.D., research assistant professor
within the Center for Musculoskeletal Research and the James P.
Wilmot Cancer Center, both within the University of Rochester
Medical Center. "Bortezomib caused osteosarcoma cells to self
destruct, and prevented their spread. While further studies are
needed, our findings suggest that this drug may represent a new
treatment option for a devastating disease and an effective
complement to current chemotherapies."
Reason to Hope
Eliseev's lab and others have shown that a protein complex
called 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 for their own self-destruction, but also
suppressed the ability of osteosarcoma cells to grow, in a two-fold
effect," Eliseev said. "The study results also give us reason to
hope that the treatment will avoid side effects, because bortezomib
induces cell death in osteosarcoma cells but not in normal
Source: University of Rochester Medical Center
CONTACT: Greg Williams of the University of Rochester Medical
Web Site: http://www.urmc.rochester.edu/
Posted: November 2009