Double drug combo

Two different drugs may work better in a "one-two punch," targeting cancer cells of two types.

A new study conducted by researchers at Johns Hopkins Kimmel Cancer Center suggests that two different drugs may work better in a "one-two punch," targeting a cancer development process in two types of cells.

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Cancer cells inappropriately remove small molecules called acetyl groups from histones, forcing the DNA to remain tightly coiled and restricting gene activation.

This error may be reversed by using drugs called histone deacetylase (HDAC) inhibitors to block the enzymes that remove the acetyl groups allowing the DNA to unwrap itself and make necessary gene products.

To test the combination, the scientists led by Roberto Pili chose an anti-angiogenesis drug that blocks the effect of a protein called VEGF, for vascular endothelial growth factor, which is responsible for triggering a cascade of cell signals that promote blood vessel formation.

"Such VEGF inhibitors are known to have most effect on endothelial cells, the bricks and mortar of blood vessels. However, HDAC inhibitors target both endothelial and epithelial cells, which line organs, and are the origin of many cancers," Pili said.

The VEGF inhibitor combined with an HDAC inhibitor and reduced the number of endothelial cells in culture dishes by 51 percent. In mouse models, the combination controlled 60 percent of new blood vessel formation compared to 50 per cent using the agents alone.

Tumor growth in mice with prostate cancer was reduced by 35 and 75 percent for the VEGF and HDAC inhibitors, respectively while the combination of drugs reduced tumor development by 85 per cent.

Mice with breast cancer showed similar inhibition of tumors with 54 and 60 per cent growth reduction for the VEGF and HDAC inhibitors alone. In combination, the drugs slowed tumor growth by 80 per cent.