Pilot project begins work on a cancer genome atlas

Washington -- Two institutes of the National Institutes of Health are teaming up on a pilot project to characterize the multitude of genetic changes that occur with cancer. It's a large undertaking, say researchers, but one that could lead to the development of more effective treatments.

The project, called the Cancer Genome Atlas, or TCGA, will attempt to develop a comprehensive catalog of changes that can cause a healthy cell to become cancerous. These changes can include chromosome rearrangements, DNA mutations or chemical modifications of DNA that can turn genes on or off.

"The time is right to bring the full power of genomics to bear on the problem of cancer," said Francis Collins, MD, PhD, director of the Human Genome Research Institute, which, with the National Cancer Institute, is leading this effort. He and several other researchers and administrators spoke at a Dec. 13 briefing.

"One person dies of cancer each minute in the United States alone," Dr. Collins said. About 570,000 people in the country died of cancer last year. "Those of us here are determined to change that."

The mapping of the cancer genome is the next step in applying the findings from the Human Genome Project, said NIH Director Elias Zerhouni, MD. "It is now possible to envision a systematic effort to map the changes in the human genetic blueprint associated with all known forms of cancer."

The project's promoters believe the availability of an atlas of genetic changes could lead to more innovative drugs, diagnostic tests for earlier detection and other tests that could guide physicians to the most appropriate treatments for patients, as well as, ultimately, new ways to prevent cancer.

"This is a revolutionary program that we are describing today," said Anna D. Barker, PhD, deputy director of the NCI. "It leverages and capitalizes on everything we've done in the last 40 years in biomedical research."

The pilot project is intended to generate in-depth portraits of between two and four tumor types. The success of the pilot will determine whether the project will go forward to look at all the different tumors.

The NCI and the HGRI have allocated $100 million for the three-year-effort, a large amount, noted federal officials, particularly during a time of NIH budget constraints. If the program continues beyond the pilot phase, the cost could reach $1 billion.

The types of tumors to be studied for the initial project have not been selected, Dr. Barker said. The goal is to choose tumors that are as homogeneous as possible from patients on standard protocols, she said. The tumors also have to be large enough to provide samples of sufficient size.

Eligible patients will be asked to donate a small portion of tumor tissue that has been removed as part of their treatment.

Hundreds of samples of each tumor type likely will be necessary, Dr. Collins said. Researchers must analyze the genetic material from numerous tumors from many patients to uncover the telltale genetic signatures of different cancer types.

"This is an audacious undertaking," he said. "It's like doing a hundred human genome projects."

Building on successes

"The goal is to really understand, for the first time, the genetic abnormalities that exist in human tumors," said Gordon Mills, MD, PhD, professor and chair of molecular biology at the University of Texas M.D. Anderson Cancer Center in Houston. Dr. Mills and colleagues intend to apply for a grant or grants to work on the project.

"What we have from the Human Genome Project is an understanding of the normal human genome, but we know that there are many changes in cancer, and this will be a comprehensive analysis of those changes in a way that has never been done before," Dr. Mills said.

But there already are therapies known to work in the presence of certain mutations, noted Bruce E. Johnson, MD, associate professor of medicine at Harvard Medical School in Boston. He spoke at the briefing.

For example, it was recently found that the 10% of lung cancer patients with mutations in the epidermal growth factor receptor are likely to respond well to the drugs Iressa (gefitinib) and Tarceva (erlotinib), which were developed in the 1990s.

Likewise, Gleevec (imatinib mesylate) is a molecularly targeted drug proven effective in the treatment of chronic myelogenous leukemia, gastrointestinal stromal tumors and several other cancers. And Herceptin (trastuzumab) has been found to be effective in the treatment of breast cancers in those with a specific genetic anomaly.

The project is not without controversy, Dr. Mills said. The drugs that have been found to work well have been identified via targeted analysis. "The controversy is whether looking globally will be as successful," he said. "And that's why this is considered a pilot in which a few tumor types will be analyzed in depth to determine whether the reward from that process is worthwhile."