Healio
Healio
April 20, 2009
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2.5-dimethyl-celecoxib targeted tumor cells, tumor blood vessels

AACR 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 Southern California.

“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-celecoxib’s potential use in the treatment of gliomas:

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 long term.

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.