Magazine article Science News

Diverse Strategies to Vanquish Cancer: Researchers Take Aim at Malignancy

Magazine article Science News

Diverse Strategies to Vanquish Cancer: Researchers Take Aim at Malignancy

Article excerpt

During World War II, scientists realized that the chemical weapon Known as mustard gas, used in World War 1, could inhibit the growth of cells. A similar substance was found to be an effective treatment for cancer, a disease in which cells aggressively divide and invade other tissues.

Thus began modern medicine's reliance upon chemotherapy.

Many chemotherapeutic agents kill cancer cells by blocking their growth However, drugs that kill a rapidly dividing malignant cell will also destroy rapidly dividing healthy cells, such as some of those in the intestinal lining, hair follicles, or blood. Thus a treatment that shrinks the tumor may also cause vomiting, hair loss, and a dangerous drop in white blood cells.

Most people would be willing to endure such ill effects if they could count on chemotherapy for a cure. Unfortunately, cancer has proved a vicious competitor.

For many people with a diagnosis of cancer, the first line of defense is surgery to remove the primary tumor. Then, to kill malignant cells that have made their way into the bloodstream, cancer specialists give a regimen of chemotherapy. This strategy generally succeeds for a while, but some cancer cells survive the chemical blast. Such cells are generally resistant to another round of chemotherapy. If they go on to form a second tumor, the cancer almost always proves lethal.

Many researchers now believe that indiscriminately blasting the body with chemotherapy is an outdated approach.

"The old way of thinking about tumor therapy is really the blitzkrieg idea--you blow out the tumor cells, and hopefully you don't take the patient with it," says Howard A. Fine of the Dana-Farber Cancer Institute in Boston.

Fine and others are focusing instead on key abnormalities that set a malignancy apart. This approach, they hope, will yield a guided missile that homes in on cancerous cells. In one such attempt, scientists are tailoring a drug to kill tumor cells that harbor a certain cancer-causing gene, or oncogene. In another, researchers have harnessed a virus to destroy cells having a certain genetic defect. In a third approach, Fine's team is blocking the tumor's voracious appetite for blood.

Although the three groups have taken different approaches, each is looking for a chink in cancer's armor.

The first group's work began with Ras genes, which are abnormal in half of all colon cancers, about 90 percent of pancreatic cancers, and smaller fractions of other human cancers. Like other oncogenes, Ras is a normal gene that, when damaged or mutated, directs the cell's machinery to manufacture a flawed protein. That abnormal protein then tells the cell to divide aggressively. Cancer can be the result.

Drugs designed to block that proliferation may prove effective against human cancer, according to a team working at the Merck Research Laboratories in West Point, Pa. These researchers searched fruitlessly for an antidote to the Ras protein for almost a decade, recalls Allen Oliff, executive director for cancer research at Merck. The company was poised to shut down the entire project in 1989, he recalls.

Then, Patrick J. Casey of Duke University Medical Center in Durham, N.C., and his colleagues showed that the cell modifies mutant Ras proteins before they send the signal to begin dividing wildly. The next year, Casey's team and several others showed that a cell enzyme called farnesyltransferase is at the heart of this malignant process. Without the enzyme, the mutant Ras protein can't instruct a cell to embark on a path of explosive growth.

The Merck team began testing a series of compounds that block farnesyltransferase. In theory, such chemicals would block abnormal cellular growth caused by mutant Ras genes.

To explore this possibility, the researchers first applied one of the chemicals to human cancer cells that carried a mutant Ras gene. …

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