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Lung Cancer May Be in the Genes

Scientists identify three genes that act as tumor suppressors

FRIDAY, May 3, 2002 (HealthDayNews) -- In what could be a significant payoff from the mapping of the human genome, Texas researchers have identified three genes on one chromosome that act as tumor suppressors and dramatically reduced human lung cancer tumors in mice.

Gene therapy trials with humans are expected to start within a year.

The study, which appears in the new issue of Cancer Research, represents 10 years of work and was partially funded by the Tenneco, Exxon, Tobacco Settlement Funds.

In healthy individuals, the three newly identified genes -- all located on chromosome 3 -- probably work to suppress or kill off any abnormal cells that appear. In individuals who have lung cancer or who are at risk for the disease, however, the genes are probably absent, the researchers suggest.

"These are normal genes that apparently control cells' life and death. What happens in lung cancer patients is that because of some interaction with cancer-causing agents, they actually get deleted from the chromosome," says Dr. Jack Roth, co-author of the study. Roth is chairman of the department of thoracic and cardiovascular surgery at the University of Texas M.D. Anderson Cancer Center in Houston.

The findings are important for a number of reasons. For one thing, the changes in this chromosomal 3p region represent the earliest genetic changes known in the process of lung cancer development. The discovery could have implications for earlier detection, diagnosis, prevention and treatment of lung cancer, which is the number one cancer killer of both men and women in America, the researchers say.

Also, this is the first time genes with a similar function have been found grouped together.

"There have been other cancer-causing genes identified in lung cancer, but they are individual genes that are scattered around the entire human genome," Roth says.

"This was very interesting because it's a very small region of the chromosome and the region contains 10 genes. And of those 10 genes, we mention that three of them had this tumor-suppressor activity grouped together. That's very unusual and hasn't been reported before, and suggests they might be working together or might be a very important area of the chromosome for preventing cancer," he adds.

Dr. Christopher Azzoli is a clinical assistant physician at Memorial Sloan-Kettering Cancer Center in New York City. He calls the new research "very exciting stuff, but it's still in the preliminary stages."

"The experiments are being conducted in cultured cells, and also in animal models, so, in that respect, it's still quite a ways off from being applicable and therapeutic to patients," Azzoli says.

The Texas researchers injected human lung cancer cells into mice intravenously and let tumors develop. The three genes (101F6, NPRL2 and FUS1) were then injected into the mice via an inactivated cold virus. They not only inhibited the growth and spread of the tumors; in some cases, they also killed off the cancerous cells.

"Not all of the mice, but some were actually cured," Roth says.

The eventual idea would be to use a similar type of gene therapy with people who have lung cancer or to find a drug or molecule to replace the actions of the gene.

"Any time you identify a new target for treatment for cancer, that raises hope," Azzoli says. "The future is probably going to be in using multiple targets because lung cancers are very complex cancers, and ultimately we will probably need more than one target to treat lung cancer."

Any new therapies could potentially be used in screening, as well as in prevention and treatment, the researchers say.

Roth and his colleagues have already submitted an investigational drug application for the FUS1 gene to the U.S. Food and Drug Administration. Once that is approved, they will begin testing what could become a new drug for people with lung cancer.

Phase I clinical trials are expected to start within a year. For humans, the gene therapy will be delivered in a fat-coated capsule rather than a regular virus.

What To Do: For more information on gene therapy, visit the National Institutes of Health Office of Biotechnology Activities. You can find more information on lung cancer at the American Cancer Society or the National Cancer Institute.

SOURCES: Jack Roth, M.D., chairman, department of thoracic and cardiovascular surgery, M.D. Anderson Cancer Center, Houston; Christopher Azzoli, M.D., clinical assistant physician, Memorial Sloan-Kettering Cancer Center, New York City; May 1, 2002, Cancer Research
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