Researchers have discovered that they can turn off the growth of cancer cells in the laboratory by inserting a gene that acts like an "off switch."

The discovery provides important new insights into the sequence of events that led to the creation of a cancer cell. It also raises the possibility of one day -- not immediately -- developing new therapies aimed at the cause of this leading killer.

The recent results have galvanized researchers trying to understand cancer's basic biology, as well as a number of pharmaceutical companies, including Hoffmann-LaRoche Inc. and Bristol-Myers-Squibb Co., which have begun searching for chemicals that can mimic the genetic "off" switch.

A drug would be easier to use than trying to repeat the laboratory experiment of putting the cancer-suppressing gene into the millions, even billions, of cancer cells in a patient's body.

Merck Sharp & Dohme recently published preliminary results with one drug that may act like an "off" switch in cervical cancer.

In addition, the discovery of this genetic off switch has created excitement among doctors treating cancer patients because the most common forms of the disease, including tumors of the breast, lung, brain, colon and bone, are missing this switch.

If a way can be found to use these off switches in patients, the discovery could help thousands of people each year, said John Minna of the National Cancer Institute.

NCI estimates that of the more than 1 million people who will develop the disease in 1990, about 463,000 will suffer from cancers of the breast, colon and lung; those three diseases alone will cause nearly half of all cancer deaths.

"These are big numbers," Minna said. Many of the previous treatment advances -- such as drugs for lymphomas, leukemias and testicular cancer -- have been for relatively rare cancers that afflict few Americans.

The current work grows out of a decade- long struggle to understand how different types of genetic damage can turn a normal cell into a cancer cell. Scientists now know that there are perhaps 50 different normal genes in the body that can be subverted in such a way that they cause cells to grow out of control.

These cancer-promoting genes -- or oncogenes -- force cells to begin growing rapidly, just as the gas pedal on an automobile causes the car to accelerate. Researchers have been searching for ways to block these cancer-promoting oncogenes, but none of the possible drugs is yet being tested in people.

Now, scientists have discovered another set of genes associated with cancer -- called suppressor genes; when they are present and functioning normally, they act like the brake on a car. When the genes are damaged or deleted, however, the cell grows out of control.

In April 1989, a group of Johns Hopkins University researchers led by Bert Vogelstein discovered that a suppressor gene called p53 was somehow lost or damaged in colon cancer cells. Scientists have since shown that p53 is also deactivated in cancers of the lung, breast, brain, bone and perhaps others.

"Various kinds of evidence suggested that the normal copy of the p53 gene might be able to suppress cell growth," acting as a genetic off switch, Vogelstein said.

The Hopkins team tested that idea by putting the p53 gene into cancer cells they had growing in the laboratory. According to their recent report in Science magazine, this gene made the cancer cells stop growing.

"This is the first time that the replacement of a normal gene has been shown to stop its {cancer's} growth," Vogelstein said. "It's a provocative experiment."

Work on this cancer-suppressing gene has heated up in the last few months.

A team led by W. Edward Mercer at Temple University in Philadelphia got the same results as the Hopkins group when it put the p53 gene in glioblastoma cells, which cause a type of brain cancer, according to a report in a recent issue of the Proceedings of the National Academy of Sciences.

The Philadelphia team, however, inserted the p53 gene into the tumor cells in such a way that the gene could be turned on and off. When p53 was turned on, the cancer cells stopped growing; when p53 was turned off, the cancer cells started growing again.

A group at the Harvard Medical School led by Stephen Friend put the p53 gene into osteosarcoma cells, a type of bone cancer, and again, the tumor cells stopped growing.

In addition, the Hopkins experiments showed that the p53 gene's braking power worked even when the colon cancer cells The National Cancer Institute estimates that of the more than 1 million people who will develop the disease in 1990, about 463,000 will suffer from cancers of the breast, colon and lung; those three diseases alone will cause nearly half of all cancer deaths.

had suffered additional genetic damage that normally accelerates cell growth.

"Even though these cells had several different gene defects that led to the cancer, just putting the p53 back in seemed to stop their growth," Minna said. This suggests that physicians may not have to repair every genetic defect in cancer cells before their growth is stopped.

How this finding will translate into a cancer treatment is not yet clear. Physicians cannot now insert a gene into cancer cells in a human patient as they can with cells in the laboratory.

"Ultimately, we would like to have a drug that we could give people that could replace {the damaged gene's} function," said NCI's Minna.

Merck, Sharp & Dohme has been attempting to develop a drug based on a suppressor gene -- called Rb -- associated with retinoblastoma, a rare, inherited eye cancer.

Researchers now believe that the papilloma virus causes cervical cancer when one of the virus's proteins blocks the braking action of the Rb gene, causing the cervical cells to grow out of control and form a cancer.

But no drug has been identified that can act like a braking gene, and none of the scientists expects that the emerging technologies of human gene therapy -- in which new genes are placed inside a patient's own cells -- can be used to attack cancer cells directly.

"Gene therapy is tricky," said Harvard's Friend. "It requires you to target every cell. There are so many cells within a given tumor that hitting them all is going to be difficult."

Even as researchers search for new ways to put the brakes on cancer growth, other reseachers have begun focusing on ways to block the genetic signals that accelerate cells to grow out of control, said Stuart A. Aaronson, a cancer gene researcher at the National Cancer Institute.

His group for example, has shown that a growth hormone gets accidentally turned on in some cancer cells, causing them to stimulate their own growth.

If a way can be found to block the growth signals, then the disease could be stopped. Researchers are now searching for a compound to do that.

Still, "this is where the new knowledge that we gained over the last few years is really taking us," said Aaronson.

"It is giving us logical approaches to designing new methods to treat cancer."