100th Annual Meeting
The compound 2.5-dimethyl-celecoxib, an analogue of celecoxib which does
not inhibit COX-2, targeted tumor cells and tumor vasculature in in vitro and
in vivo models, according to data presented at the AACR 100th Annual Meeting.
This drug may be particularly useful in tumors that are highly vascular,
such as gliomas, said Florence M. Hofman, PhD,
professor of pathology at the Keck School of Medicine at the University of
Currently, the major treatment for gliomas is temozolomide
(Temodar, Schering). We know from our studies that temozolomide is very
effective in killing glioma cells, but it does not affect the tumor
vasculature, Hofman said.
However, 2.5-dimethyl-celecoxib, or DMC, targets both the tumor and
endothelial cells without the cardiovascular side effects of COX-2 inhibitors.
We found that DMC causes glioma cell death and cytotoxicity of the
tumor vasculature, but not the normal vasculature, Hofman said.
A study of DMC in animals showed smaller tumors and fewer blood vessels
in the tumors with a 35% to 40% reduction in blood vessel density.
We know that other tumors are also highly vascular, so this
therapeutic drug could be used in other tumors as well as gliomas, she
said. by Leah Lawrence
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Florence M. Hofman,
PhD, comments on 2.5-dimethyl-celecoxibs potential use in the treatment
We need to have an antiangiogenic therapy in combination
with temozolomide, the current therapy for brain tumors. The antivascular drug
which is FDA approved, has many side effects, and cannot be tolerated over the
DMC has no significant cardiovascular side effects and can
be administered for long periods of time. These are essential drug
characteristics for treatment of brain tumors.
Many scientists believe that cancer, especially brain
cancer, will be treated as a chronic disease, with long-term treatment. Though
it is not a cure, this approach may provide the patient with years of disease
free living, instead of months.
At this point we are testing DMC in rodent models, but
hopefully we will soon begin phase-1 trials in humans. We expect that DMC will
be useful in treating gliomas and other metastatic tumors to the brain.