Scientists Map Genetic Codes for Breast, Colon Cancers

Step lays groundwork for better, targeted treatments, experts say

THURSDAY, Sept. 7, 2006 (HealthDay News) -- In what experts are calling a milestone achievement, U.S. researchers have sequenced the genetic "blueprints" of two major cancer killers -- breast and colon cancer.

Identifying nearly 200 genes thought responsible for these diseases, the work gives researchers new insight into these malignancies and lays the foundation for the gene-targeted therapies that may one day cure them.

"Only by understanding this blueprint of cancer will we be fully able to understand the mechanism of what makes a cancer a cancer and to think about strategies for diagnosis, prevention and therapy," explained Dr. Victor Velculescu, senior researcher on the project and an assistant professor of oncology at Johns Hopkins University's Kimmel Cancer Center.

Experts elsewhere were similarly optimistic. In a statement, Dr. Elias A. Zerhouni, director of the U.S. National Institutes of Health, which funded the project, described the new genetic maps as "groundbreaking work."

"This research approach holds great promise for providing an understanding of the genomic contributions to cancer," he said.

Velculescu's team outlined the findings in the Sept. 8 issue of the journal Science.

Just as the human body has its genetic code, so, too, do cancer cells.

"Work from the past two decades has shown us that cancer is a genetic disease," said Velculescu. He explained that a malignancy occurs when specific genes in healthy cells undergo unhealthy mutations.

"A mutation is really like a typo in a blueprint that's 3 billion letters long," he said, so spotting any one mutation has been like finding the proverbial needle in a haystack.

A new $100 million federal initiative, The Cancer Genome Atlas project, seeks to change all that by mapping the myriad genetic "typos" that cause specific tumor types to form. The project described in Science is the first major step in that effort.

In their research, Velculescu and his colleagues from across the United States focused on cracking the gene codes for breast and colon cancers, which together make up one-fifth of all cancer diagnoses worldwide. Other initiatives, focused on other tumor types, are currently under way.

The team analyzed more than 13,000 genes from tumor tissues taken from 11 patients with breast cancer and 11 patients with colorectal cancer.

What they found surprised them.

"Many of us might have expected that only a few of the 'building blocks' in a cell to be mutated, but we actually found quite a number of them," Velculescu said. "It looks like each cancer has about 100 different genes that are mutated, at least 20 of which are thought to be important for the tumor's progression."

The research also confirmed that there's no one disease called cancer.

"It looks like there are quite a bit of differences between the blueprint of different cancer types," the Johns Hopkins expert noted. "Colon and breast cancers are different, and, in addition, each individual's cancer is different. This, in part, may explain the differences that clinicians for a long time have seen among their cancer patients."

But the team also found "commonalities" between colon and breast cancers as well -- mutations that affected similar cellular pathways. "As we learn more and more about how these genes interact, about pathways and how these genes control processes that occur inside cancer cells, we may be able to find simpler [treatment] targets," Velculescu said.

Another expert agreed. "This achievement is important because, to the degree that those genes are proven now to be related to the cancer process, they provide targets that can be potentially used either for diagnostic or treatment purposes," said Dr. Len Lichtenfeld, deputy chief medical officer at the American Cancer Society.

For example, doctors may someday use sensitive nanotechnology early detection tests to spot tiny amounts of cancer-linked proteins produced by these aberrant genes. "That would be a test that would enable you to diagnose a cancer long before you are actually able to see it," Lichtenfeld said.

In terms of treatments, drug developers can target specific genes and their proteins to create treatments that stop a cancer cold without harming the patient. Gleevec -- the "wonder" drug now used to halt chronic myelogenous leukemia -- is one such targeted therapy, Lichtenfeld said.

"So, this new achievement is a really important step and an important link between where we are today and where we have been talking that we will be in five, 10, 15 years," he said.

Velculescu said he shares that vision.

"We are predicting that cancer is an individualized disease, and there will come a day when people will go into the clinic and their tumor will be analyzed for specific mutations," he said. "Based on the combination of genes that are mutated, they will receive a particular combination of therapies that will treat the disease."

"We're not there yet, and there's still a long way to go," Velculescu said. "But without knowing what's broken inside a cancer cell, we have no hope of fixing it."

More information

For more on gene therapy and cancer, head to the American Cancer Society.

SOURCES: Victor Velculescu, M.D., Ph.D., assistant professor, oncology, Johns Hopkins Kimmel Cancer Center, Baltimore; Len Lichtenfeld, M.D., FACP, chief, American Cancer Society, Atlanta; Sept. 7, 2006, news release, U.S. National Institutes of Health; Sept. 8, 2006, Science
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