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Vantage: Cancer Breakthrough
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Poised for a Cancer Breakthrough

Dr. Harold Moses believes the accelerated rate of discovery into the genetic basis of cancer will soon yield treatments and cures.

The recent discovery that the uncontrolled growth of cancer cells is due primarily to a malfunction in two sets of genes that operate as "on-off" switches has a pioneer in the field of cancer research optimistic about the prospects for conquering the insidious disease.

Harold L. Moses, M.D., Benjamin F. Byrd professor of oncology and director of the Vanderbilt Cancer Center, cites the identification of oncogenes and tumor suppressor genes as major findings on the path to a cancer cure.

Oncogenes are normal genes altered by a mutation that creates an abnormal increase in their activity. Tumor suppressor genes, on the other hand, normally inhibit cell growth, but they lose that capacity if they are either altered or absent. Either the creation of oncogenes or damage to the tumor suppressor genes allows cells to proliferate as cancerous growth.

How were the two sets of genes discovered? Researchers growing cells in the laboratory observed that in some cases cells "no longer acted respectful of their neighbors as normal cells do, but began behaving like cancer cells, growing on top of each other," says Dr. Moses. "When researchers identified the piece of human genetic material causing this, oncogenes were discovered." To date, about 70 oncogenes have been identified.

The tumor suppressor genes were discovered by identifying (cloning) genes absent in certain human cancer cells. One tumor suppressor genes produces a protein known as p53. Its function is to allow a cell that has suffered damage to the genetic material in the chromosomes to repair itself before dividing into two new cells. In this way, damaged genetic material is not passed on.

The "elegant mechanism" of p53 function was discovered in studies with mice. When p53 was removed from the fertilized eggs of mice, the mice still grew but began developing cancer at an early age. "It may take 10 or more lesions in a chromosome (where genes are tightly wrapped) to cause a cancer," explains Dr. Moses, "but having a defective tumor suppressor gene that fails to manufacture p53 will allow the damage to accumulate, leading in time to cancer." In humans the latency period can be from 10 to 30 years.

Dr. Moses sees genetic cancer research producing broad benefits. For example, since the p53 mutation and mutations in other tumor suppressor genes and oncogenes can be detected, individuals with the mutant genes can be considered for preventive therapy or advised to make lifestyle changes that will offer them more protection from cancer, he says. For individuals who have already accumulated damage to chromosomes, gene therapy hold promise. "If the proper mechanism is devised, we will be able to insert a healthy tumor suppressor gene to make the cell behave more normally," he explains. And even better than intervention will be cancer prevention, "the ultimate payoff of the research," Dr. Moses says.

"What we have learned about cancer as a genetic disease in the past 10 years is incredible, and 80 percent of that knowledge has been gained in the past five years," says Dr. Moses, past president of the American Association for Cancer Research.

"We're learning a lot about how a cell works, and the rate of discovery is rapidly accelerating," he adds. "Everyone in the field is optimistic about a breakthrough. We know it's coming."

Copyright © 1996, Informatics Center, Vanderbilt University Medical Center

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