Pharmaceutical 'smart bomb' targets cancer cells

December 31, 2000

NEW BRUNSWICK/PISCATAWAY, N.J. - Rutgers pharmaceutical chemist Longqin Hu and his colleagues have developed a new series of compounds for drugs that have the potential to attack cancer like a high-tech "smart bomb." This high-powered combination of a novel cell-killing agent and a precision targeting technology proved to be as much as 100 times more potent than a comparable drug currently in clinical trials.

"We are testing this combination and it looks like a winner," said Hu, an assistant professor at the Ernest Mario School of Pharmacy at Rutgers, The State University of New Jersey.

The delivery of the compound is accomplished with a prodrug - an inert chemical derivative of a drug that can be activated once it reaches its destination inside a patient's body. Prodrugs can transport highly potent medicines such as Hu's cytotoxins (cell-killers), without impacting other body tissues along the way. Hu's research employs a new and improved prodrug package developed by collaborators in England.

This dramatic step in the march toward a cancer cure will be featured twice during the 226th American Chemical Society (ACS) national meeting in New York. Hu is presenting a paper on Monday, Sept. 8 at 3:45 p.m. in the Javits Convention Center, room 1E02. In addition, Hu and his colleagues are exhibiting at a poster session on Wednesday, Sept. 10 in the Hilton New York, Americas Hall 1 from 6 p.m. to 8 p.m.

Traditional anticancer drugs use accelerated cell growth as their trigger, which can produce collateral damage in rapidly replicating normal cells. "That is how you wind up with the negative side effects you see in chemotherapy patients, such as hair loss, nausea and reduced immunities," said Hu.

Instead of hitting all cells that grow fast, the newly reformulated prodrugs use a protein or enzyme as the activating trigger, guaranteeing a direct hit on cancerous cells. Nitroreductase - an enzyme not normally found in the body, not even in cancer cells - is used as the activator. When researchers insert a gene for this enzyme into cancer cells, the cells start to express the nitroreductase, making them an easy target. The prodrug "bomb" goes off and unleashes the toxin that spreads to neighboring cells which ultimately kills the tumor.

The English contingent also developed a compound that is being evaluated in clinical trials as an anticancer prodrug. But Hu's new compounds appear to be even more potent. The overseas researchers are now testing the Rutgers compounds, side by side with their own, delivering them in the enhanced prodrug packages.

Initial testing on mammalian hamster cells shows that after 72 hours of drug exposure, the Rutgers compounds were as much as 100 times more effective in inhibiting cell growth. One-hour tests were also performed and, again, the Rutgers compounds were found to be superior - as much as 30 times more effective than the English compound. Eighteen-hour tests on human ovarian cancer cells showed a still significant, tenfold superiority.

"Our cytotoxic compounds delivered to the cancer site in a revamped prodrug form clearly show great potential, but there are still lots of tests to be done," said Hu. "There are many preclinical studies ahead of us. If everything goes well, we could see clinical trials in humans in a couple of years."

Hu says that these compounds are not going to cure cancer by themselves. But they will be significant tools, most probably used in combination with other technologies - one bullet of many in the arsenal of anticancer weapons.
-end-


Rutgers University

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