Hitting enzymes to kill cancer cells.

Hitting enzymes to kill cancer cells 

Going beyond treating the whole tumor, scientists are looking for fine-tuned drugs that attack the inner workings of cancer cells. Among the latest of these efforts is the inhibition of DNA topoisomerases -- enzymes needed to alter DNA's structure before synthesis of RNA and new DNA can occur. Scientists at the University of Florida in Gainesville are using a computer modeling system to make unique anti-enzyme drugs. And in doing so, they have resurrected a once-abandoned cancer treatment.

Speaking last week at the American Association for Cancer Research's annual meeting in New Orleans, Warren E. Ross said his group compared the structures of drugs already known to inhibit the enzyme topoisomerase II. Discovered within the last decade, the enzyme helps untangle DNA and may direct DNA arrangement in chromosomes (SN: 2/23/85, p.120). From these studies, Ross says, it became apparent the drugs bind first to DNA and then entrap the enzyme. The Florida researchers found that the higher the enzyme concentration, the more potent the drug, and that adding specific chemical groups onto a drug molecule enhances its inhibitory activity.

The researchers also found that a previously tested drug called camptothecin works by inhibiting topoisomerase I -- knowledge that has led to an improved version of the drug. Thus far, Ross says, the new camptothecin has worked well against leukemia and several solid tumors in mice, with "predictable and manageable" toxicities, and without the drug resistance so often developed by cancer cells.