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 2008.
"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 bone-making cells."
SOURCE University of Rochester Medical Center
Greg Williams of the University of Rochester Medical Center, +1-585-273-1757
