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MARKETPLACE:  Auto | Jobs | People Search | Personals | Travel | Yellow Pages  November 24, 2004
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Key Protein in Breast, Ovarian Cancer Found
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By Amanda Gardner, HealthDay Reporter

MONDAY, Oct. 25 (HealthDayNews) -- Researchers have identified a protein which, when present in large amounts, might indicate that a cancer is particularly aggressive.

The protein, Rab25, could end up serving as both a predictor of prognosis for ovarian and breast cancer and a target for future treatments.

"It could be both diagnostic and therapeutic. That's unusual," said Dr. Julia Smith, associate director of the cancer screening and prevention program at New York University Cancer Institute and director of the Lynne Cohen Breast Cancer Preventive Care Program, both in New York City. Smith was not involved in the study, which appears in the November issue of Nature Medicine.

Even with current therapies, the compound could find a role to play. "If you don't have an aggressive cancer, you may not need more therapy," explained study author Dr. Gordon Mills, chairman of the department of molecular therapeutics at M.D. Anderson Cancer Center in Houston. "If you identify a cancer as aggressive, you might use different types of therapy. Even if you are not targeting this protein specifically, you may manage the patient differently."

The researchers discovered that there are extra copies of the gene that produces Rab25 in some breast and ovarian tumor cells. This leads to extra production of the Rab25 protein itself.

When they analyzed tumor samples from about 100 patients with either breast or ovarian cancer, they found that patients with low levels of Rab25 had better outcomes. For instance, patients with early-stage ovarian cancer who had low levels of the protein had an 80 percent chance of surviving five years after treatment, compared with a 50 percent survival rate if levels of Rab25 were high.

In women with advanced stages of breast cancer, low levels of Rab25 were associated with a 60 percent five-year survival rate, vs. 40 percent when Rab25 levels were higher.

The finding also revealed that breast and ovarian cancer are more similar than scientists had expected, Mills added.

"They may have isolated an area that will have some common applications in cancer biology, not just this tumor or that," Smith added. "It tells us a lot about tumor biology and tumor suppression, as well as proliferation, and it may give us some kind of peek into this commonality that we think exists across cancer types."

At this point, the researchers only have a partial picture of how the protein works. "We are still working on the mechanism, but the first thing that we know is that it plays a role in how molecules are recycled into the cell and then back to the cell surface," Mills explained. "This is important because a number of tumor suppressor genes work by altering that process. This seems to be another one of those in that pathway."

"The whole family [of compounds] is very interesting because of the way they interact with these transport mechanisms back and forth from the surface of the cell to the inside of the metabolic machinery," said Dr. Anthony Hoffman, president of the Eastchester Center for Cancer Care and attending physician at Montefiore Medical Center and Albert Einstein College of Medicine, all in New York City. "If you could target those, you could introduce a medicine and be able to bring it in to where the metabolism of the cell is going on, thereby overcoming some of the resistance. Also, if you could inhibit it, then you could theoretically prevention the growth signals of the cell."

Although those things are still a ways off, the act of finding the protein's role in predicting the virulence of cancer could debut in as little as a year, Mills said.

Finding drugs to attack it will take longer. "In itself, it is probably not going to be a good target, but there are molecules that regulate its function that may be a good target," Mills said.

And when that happens, it may give hope to those 25 or 30 percent of patients who are currently resistant to most therapies, Hoffman said. "These are the types of proteins we are looking for when we are treating patients," he explained. "It's looking at a patient population from a biochemical point of view -- not the way we've been looking, from a pathological point of view."

Only time will tell if this is the way of the future.

"It's a very small number of patients, but I think that would be worthwhile pursuing in a larger group to see if it holds out," said Dr. Jay Brooks, head of hematology/oncology at the Ochsner Clinic Foundation in New Orleans. "Periodically, various tumor prognostic markers come along. Whether or not they hold up remains the question."

More information

Visit the National Cancer Institute (www.cancer.gov ) for more on breast cancer.

SOURCES: Gordon Mills, M.D., Ph.D., professor and chairman, department of molecular therapeutics, M.D. Anderson Cancer Center, Houston; Jay Brooks, M.D., chief, hematology/oncology, Ochsner Clinic Foundation, New Orleans; Anthony Hoffman, M.D., president, Eastchester Center for Cancer Care, and attending physician, Montefiore Medical Center and Albert Einstein College of Medicine, all in New York City; Julia Smith, M.D., Ph.D., associate director, cancer screening and prevention program, New York University Cancer Institute, director, Lynne Cohen Breast Cancer Preventive Care Program, and clinical assistant professor, New York University School of Medicine, all in New York City; November 2004 Nature Medicine

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