December 17, 2008 Thompson

By Kate Stinchfield
WEDNESDAY, Dec. 17, 2008 ( – The chances of surviving ovarian cancer appear to vary dramatically depending on the levels of two tumor proteins, suggesting that this type of cancer may have a more nuanced outlook than the grim statistics indicate.

Women who had ovarian tumors with high levels of the two proteins survived for a median of 11 years or more, while those with lower levels survived for a median of about 2.6 years, according to a study published Thursday in the New England Journal of Medicine.

The proteins, known as Dicer and Drosha, could help guide treatment or lead to new types of therapy. They are key players in RNA interference (RNAi), a naturally occurring system that turns genes on and off. The study is the largest to link RNAi with cancer survival rates, and the researchers also found that high Dicer levels are linked to survival in breast and lung cancer.

About 22,430 new cases of ovarian cancer were diagnosed in the United States in 2007, according to the American Cancer Society. Ovarian cancer is often called the "silent killer" because it can be difficult to catch early.

In the new study, Anil K. Sood, MD, of the University of Texas M.D. Anderson Cancer Center, in Houston, and colleagues analyzed tissue from 111 women with advanced epithelial ovarian cancer, specifically looking for Dicer and Drosha. They found 60% of the cancers had low levels of Dicer, 51% had low levels of Drosha, and 39% had low levels of both.

These two proteins are responsible for cutting and shaping tiny snippets of genetic material known as microRNAs, or miRNA. In the past decade, scientists have discovered that these naturally occurring snippets are important for turning genes on and off, controlling cell growth, and determining whether cells live or die. The entire process is known as RNAi, and when the system is damaged it can lead to disease. In fact, RNAi is abnormal in just about every cancer that researchers have examined.

"In the past, people used to think that miRNA might actually promote tumor growth, but there is some emerging thought that some of the miRNAs might keep tumors from growing and actually function as a tumor suppressor," says Dr. Sood, who is an associate professor of cancer biology.

Many biotechnology companies are now trying to exploit this lock-and-key mechanism to fight other diseases. They have created synthetic molecules, called small interfering RNAs (siRNAs), which are being tested as a way to treat age-related macular degeneration, an eye disease, and many other conditions. "RNA interference is a way of shutting off or controlling genes," Dr. Sood explains.

However, the research doesn’t have an immediate application for the treatment of women with ovarian cancer. "Should somebody go out and have this checked? No, not at this point," says Dr. Sood. "'But this is guiding us in developing appropriate therapies for the average person."

The finding may eventually help doctors determine if an ovarian cancer patient needs more aggressive treatment. The researchers found that cells with inadequate levels of Dicer couldn't turn genes off.

"We now know that ovarian cancer patients with low levels of these proteins tend to fare worse," says Dr. Sood. "Now we can use this evidence to target treatment."

The study may also help scientists create designer drugs to treat patients with cancers that have low levels of Dicer and Drosha. "This really helps us to understand more about the fine-tuning mechanisms that are going awry in cancer cells versus normal cells," says Robert J. Morgan Jr., MD, codirector of the gynecological malignancy program at the City of Hope Cancer Center, in Duarte, Calif. "While this won't influence patients right now, it will influence scientists developing these lifesaving drugs."

But how long does that take? It's difficult to estimate, but researchers have made significant leaps in cancer care over the past decade. "Ten years ago, there were no designer drugs. Now there are probably 25 or 30, with literally hundreds in the pipeline," Dr. Morgan says. "I wouldn't be surprised if we didn't see some direct progress here in just a couple of years."

Related Links:
Cranberries Fight Ovarian Cancer
Breast and Ovarian Cancer (BRCA) Genetic Test
Help Fight Ovarian Cancer
Decoding the Genetics of Ovarian Cancer

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