LEXG It's studies like the following that will make LEXG a powerhouse(they have to use the genomic discoveries on mice data pool and LEXG is the leader) New York Times August 18, 2000 Gene Study Highlights Lack of Tumor Knowledge By REUTERS
ASHINGTON -- Scientists said Thursday they had found dozens of new genes involved in the process tumors use to feed themselves, offering many potential new targets for cancer therapy.
They said they were surprised to see just how many genes are involved in building tiny blood vessels -- most of them genes that were unknown before.
"This gives us a whole bunch more of potential targets for cancer therapy," Brad St. Croix of Johns Hopkins University in Baltimore said in a telephone interview.
"But it is going to take several years to figure out which of these are going to be useful."
The researchers used a technology they developed and licensed to Genzyme Molecular Oncology called Serial Analysis of Gene Expression (SAGE) to identify 79 genes that behave differently in tumor vessels than they do in normal blood vessels.
The process of building new blood vessels, called angiogenesis, is a new star in cancer research. Several new drugs are being tested that are aimed at starving tumors by choking off their blood supply.
St. Croix, whose study is published in the journal Science, said it showed just how little was understood about the process. "We had no idea what to expect at the start of the study, if these markers even existed," he said.
"There is only a lot of suggestive evidence. For example, it was known that vessels in tumors did not look like normal vessels at all. They are tortuous, they are kind of randomly oriented. They lack the surrounding smooth muscle cells that are characteristic of normal vessels."
So the Johns Hopkins team used the SAGE technology to see what was different about the tumor blood vessels.
They took tumors from a colon cancer patient and teased out the endothelial cells that lined the blood vessels feeding the tumor. As a comparison, they looked at endothelial cells from normal, healthy colorectal tissue from the same patient.
Technology Finds Turned-On Genes
SAGE helps identify the active genes in a tissue sample. Most cells contain all the genes that a person has, but sometimes they are expressed, or turned on, and sometimes they are not, depending on the cell type.
The team identified 46 genes that were unusually active, or over-expressed, in the tumor tissue and 33 genes that were expressed at unusually low levels.
"The majority of them were novel," St. Croix said.
Now the researchers are trying to identify these genes. Genzyme, which employs some of the Johns Hopkins team as consultants, is as well.
"We need to do some additional work on those to be able to understand whether they are good targets for inhibiting angiogenesis," Gail Maderis, president of Framingham, Massachusetts-based Genzyme Molecular Oncology, said in a telephone interview.
St. Croix said his team found the same genetic pattern in brain, breast, lung, pancreatic and other tumors.
Many companies are working on angiogenesis inhibitors for treating cancer. They involve a variety of different proteins.
"They work great in mice, but whether they work in humans is a completely open question," St. Croix said. He said his team was now checking to see if mouse tumors showed the same genetic pattern as the human tumors.
Whole New Cancer Market
Medaris said her company would use the findings as a basis for developing anti-angiogenesis weapons.
"You could think of an antibody linked to a toxin or a radioactive compound," she said.
"It's a whole different approach to treating cancer and it could be as big as the chemotherapy market is today. We believe that, just like the chemotherapy that is used in combination today, anti-angiogenesis factors will be used in combination. There is room for more than one player in that field."
Medaris said the study was a good illustration of how the budding science of genomics -- studying all the genes in the body -- can be useful.
"The question is how do you get from vast amounts of genomics data to drugs. This is an exquisite example of using genomics as a tool. We have gone from 32,000 genes expressed in endothelial cells to having isolated 46 which may be very relevant, and that is a manageable number to work with." |