Experimental Drug Destroys Liver Cancer

Animal study shows it starves, shrinks tumors that have spread

MONDAY, July 15, 2002 (HealthDayNews) -- An experimental drug with a taste for energy-thirsty cells appears to kill off liver tumors in rabbits.

Johns Hopkins University scientists found the chemical, known as 3-bromopyruvate, destroys liver cancer and also shrinks tumors that have spread from that organ into the lungs. The substance, which is related to a molecule that occurs naturally in the breakdown of sugar, starves cancerous cells of energy, but appears to leave healthy tissue alone.

The researchers say they must confirm the drug's lack of toxicity to normal tissue before they test it in people. However, they add, if it does prove benign, it might offer doctors a promising new therapy for other forms of tumors.

Liver cancer, which has been linked to the hepatitis B virus, strikes about 16,600 Americans a year and accounts for roughly 1 percent of tumor deaths in the United States. However, it's much more common in Asia and Africa, where it makes up half of all cancer fatalities.

About 50 percent of patients can be cured of the disease. However, for those with inoperable liver cancer, especially tumors that spread from the colon, surviving a year is a feat.

A unique feature of liver tumors is that while they draw their nutrients from an artery, the organ itself is fed separately by the portal vein. In theory, it's possible to target cancerous cells by injecting drugs directly into arterial blood, yet do minimal damage to the surrounding organ.

The latest study, published in today's issue of Cancer Research, attempts such a strategy.

Led by radiologist Dr. Jean-Francois Geschwind, the scientists gave injections of 3-bromopyruvate to rabbits with liver cancer.

The potent chemical drains cells of their energy in two ways: by greatly suppressing their ability to use glucose for fuel; and by hindering the ability of internal power plants called mitochondria to make the energy molecule adenosine triphosphate, or ATP.

Because cancer cells are lusty for glucose, needing it to support their frenetic growth, a drug that selectively kills tissues that demand sugar will turn this thirst against them.

Indeed, a single injection of the drug into the artery supplying the tumors led to "dramatic" shrinkage of the masses, Geschwind says.

"By being able to thread a catheter and get close to the tumor, we can deliver agents in much higher concentrations directly to the tumor. You can really kill the tumor that way," he adds.

Surprisingly, the healthy cells were spared.

"We would have expected some collateral damage, but in this case the specificity of the drug and the method of administering it made a perfect marriage," Geschwind says.

The treatment was gentler on normal cells than a current therapy for liver cancer called chemoembolization, in which doctors inject drugs into the tumors while using an oil solution to block off the artery that feeds them.

Some of the rabbits developed liver cancer nodules in their lungs. So the researchers then injected 3-bromopyruvate directly into their bloodstream through a vessel in their ears. Again, the tumors shrank markedly, but the animals appeared otherwise unscathed, says Peter Pedersen, a Johns Hopkins biochemist and a co-author of the study.

"We didn't find problems with toxicity, but we don't know what the long-term [outlook] is," Pedersen says.

If 3-bromopyruvate ultimately passes the safety tests, Geschwind says it could be useful against a wide range of tumors, because all have the common feature of requiring heaps of energy.

However, finding as finely tuned a way to deliver the drug as is possible with the liver will be trickier, he adds.

What To Do

To learn more about liver cancer, check out the American Liver Foundation or the Allegheny General Liver Cancer Program.

SOURCES: Jean-Francois Geschwind, M.D., associate professor, radiology, and director, interventional radiology, Johns Hopkins Medical Institutions, Baltimore; Peter Pedersen, Ph.D., professor, biological chemistry, Johns Hopkins University, Baltimore; July 15, 2002, Cancer Research
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