Genome project tackles cancer

NIH officials earmark $100 million for study of malignant tumors at molecular level


WASHINGTON -- In a bold but uncertain bid to spur cancer treatment, federal medical researchers announced yesterday a $100 million project to begin cataloging the disease's molecular underpinnings.

The Cancer Genome Atlas, as the project is called, will start as a three-year pilot identifying the genes behind two or three types of cancerous tumors. If the research proves promising and affordable, it would be expanded to study thousands of cancerous tumors.

Describing the effort as potentially "revolutionary," officials at the National Institutes of Health asserted that the resulting knowledge could quickly lead to the development of more effective cancer drugs and therapies.

"This is really the beginning of an era," said Dr. Elias A. Zerhouni, director of the NIH, the government's main medical research arm and a distributor of funding. "What I think we will see is an acceleration of discovery."

Often referred to as a single disease, cancer is actually a collection of more than 200. Cancers develop, scientists believe, after genetic changes cause cells to mutate and grow wildly.

The cancer project, NIH officials said, would find the common features underlying the genetic malfunctions -- most likely not a single glitch causing various cancerous cells to flourish, but perhaps a set of glitches that each leads to a number of diseases.

"It will be an important step in our understanding of the genetic components of cancer and the genetic susceptibilities of people affected by cancer," said Dr. Andrew C. von Eschenbach, director of the National Cancer Institute and acting head of the Food and Drug Administration.

In 2003, scientists finished mapping the human genome, the genetic code that guides a body's functions and characteristics.

Sequencing cancer genes is a natural follow-up because researchers can use the blueprint of normal human DNA to identify cancer genes. They can also capitalize on the mapping technologies already developed.

Supporters of the cancer project argue that the vast diversity of cancer genes requires NIH involvement. They say that more effective treatments can't be developed without the better understanding that sequencing cancer genes would provide.

"The more we learn about cancer at the molecular level, the more chance we have of being successful in treating cancer," said Dr. Bob Strausberg, vice president for human genomic medicine at the J. Craig Venter Institute in Rockville, founded by the scientist who raced against the government to be the first to log the human genetic code.


But the sequencing of cancer genes also presents its own challenges.

The work is costly. Because cancer causes the cells to mutate, each tumor cell has its own genome, so mapping every tumor would be equivalent to undertaking scores of human genome projects -- as many as 12,500, by one estimate.

"There are many technical problems we have encountered, and acquiring the right sample collections is always problematic," said Dr. Michael Stratton of the Wellcome Trust Sanger Institute in Britain, which studies cancer genes.

Researchers must also review many genes before distinguishing those that play important roles in causing mutations. "Sorting the `passengers' from the `drivers' is a significant issue," Stratton said.

Another obstacle is that no two cells in a malignant tumor might be identical. As a result, successful sequencing of some cancer genes might miss others. If a missed gene plays a key role in causing malignancy, treatment would suffer.

For that reason, Dr. Garth R. Anderson, a cancer geneticist at the Roswell Park Cancer Institute in Buffalo, N.Y., criticized the project for taking money from what he said was more worthwhile research promising early diagnosis of tumors and more lasting treatments.

"Focus your efforts on that direction, not on finding `miracle' targets and then `miracle' drugs," Anderson said.

NIH, he said, is "putting a lot of effort into something that I don't think will accomplish much therapeutically."

There has been some progress, however. A number of private institutions have been mapping cancer genes. And the research has led to the development of several drugs, such as Novartis Pharmaceuticals Corp.'s Gleevec, which has proved successful in treating a form of leukemia.

During research into colon cancer gene mutations, Dr. Victor Velculescu, an assistant professor of oncology at Johns Hopkins, has uncovered some common features with breast, gastric and brain cancers.

Velculescu described identifying cancer genes as a crucial but doable first step in learning about the mechanisms driving cancer. "The much harder part will be understanding what the genes do and designing drugs," he said.

Outlining the pilot project, Dr. Francis S. Collins, director of the National Human Genome Research Institute, said the intent is to fund potentially promising research into two or three types of tumors, such as colon cancer and leukemia.

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