Scientists: Genes Found That May Slow Lung Cancer
WASHINGTON (Reuters) - Scientists said on Wednesday they had discovered three genes involved in lung cancer and when they replaced the genes in mice the cancer stopped spreading and in some cases was cured.
Based on these findings, researchers said they hoped to begin gene therapy experiments in lung cancer patients within a year.
The three genes not only slowed the growth and spread of lung cancer tumors, but seemed to cause them to die off, the researchers, at M.D. Anderson Cancer Center and the University of Texas Southwestern Medical Center in Dallas, report in this week's issue of the journal Cancer Research.
The three genes, called 01F6, NPRL2 and FUS1, are all found on the same region of chromosome 3, said Dr. Jack Roth of M.D. Anderson, who helped lead the study.
"If you analyze the DNA in lung cancers you find that pieces of this chromosome are missing in many lung cancers," Roth said in a telephone interview.
"It is about the most common area for missing DNA that you can find in lung cancer."
Smoking is the main cause of lung cancer, the leading cancer killer in the world.
Smoking seems to damage this area of the chromosome very early on, Roth said. "You even see it in cells lining the trachea and the bronchial tubes that look completely normal in patients who are heavy smokers," Roth said.
Some people seem to have more delicate chromosomes than others, the researchers found, which could explain why a few people seem to be able to smoke without developing cancer.
Ten years ago, Dr. John Minna of the University of Texas identified this delicate region of the chromosome, which is also involved in many cases of breast cancer.
"It is only with advances in human genome sequencing that we identified these three genes," Minna said in a telephone interview.
"We thought we were just going to find one gene and amazingly, there are probably going to be four or five genes in this area that are tumor suppressor genes."
Replacing these missing genes, which instruct cells with faulty DNA to self-destruct, should stop the cancer.
Roth and his team found gene therapy could slow the tumors in mice and, in some cases, cure the mice of lung cancer.
They injected human lung cancer tumors into mice bred to lack proper immune systems. Such mice easily develop human cancer tumors and are commonly used in cancer research.
"You can do several things -- you can grow the tumor and just inject the gene into the tumor and it will regress," Roth said. An intravenous infusion of the genes also shrank tumors, even those that had metastasized or spread, Roth said.
GENE THERAPY TRIALS TO START
The results are so impressive that Roth and Minna's team has won permission from the U.S. National Institutes of Health committee that monitors gene therapy to start experiments in cancer patients. Roth said the team is now waiting for approval from the Food and Drug Administration.
"Because this is a Phase I study, we are interested in toxicity, side effects and safety," Roth said. Only patients with advanced lung cancer will be experimented on at first.
Gene therapy has been under a cloud since the death in 1999 of an 18-year-old gene therapy patient. The government has cracked down on researchers, who are now aware that what seemed like a very safe approach may in fact be dangerous.
Often a virus is used to carry the new genes into a patient. But Roth said his team had developed what they hope is a safer method.
They have encased the DNA for the FUS1 gene in a lipid, or fatty covering. This will be infused into the patients intravenously.
If it seems safe, they will advance to trials that test whether it can actually affect the cancer. "We are going to work on one of these genes and the ultimate goal would be to use a combination of genes," Minna said.
He said it might also be possible for someone to devise a drug that replaces the function of the genes.
Minna said a test that looks for the missing genes might also be used to diagnose lung cancer in smokers. "What is frightening is that even if someone stops smoking, 40 years later we can still find these abnormal (genes)," he said.