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Low Levels of 2 Enzymes in Ovarian Cancer Cells Shortened Survival
Date:12/17/2008

Finding could lead to new treatments for this deadly disease, researchers say

WEDNESDAY, Dec. 17 (HealthDay News) -- Women with ovarian cancer who had low levels of either of two enzymes associated with their tumors tended to die much sooner than women who had higher levels of one of the two enzymes, new research shows.

The prognosis was even bleaker for women with low levels of both proteins.

"If there were low levels [of both proteins], those patients tended to survive, on average, 2.66 years compared to those with high levels of both proteins, who survived around 11 years, so there's quite a bit of difference," said study senior author Dr. Anil K. Sood, a professor in gynecologic oncology and cancer biology at the University of Texas M.D. Anderson Cancer Center in Houston. The report was published in the Dec. 18 issue of the New England Journal of Medicine.

This information could not only help predict survival, it might also lead to treatments for the disease, which is the second most lethal cancer in women in terms of number of cases diagnosed.

"There's a spectrum of survival among patients with advanced ovarian cancer, and researchers are trying to see if there are actual genetic factors within these tumors identified that are independent from known factors such as age, stage at diagnosis, microscopic appearance of the tumor, that have an influence on the aggressiveness of the tumor," said Dr. Robert A. Burger, co-director of the Ovarian Cancer Research Program at Fox Chase Cancer Center in Philadelphia. "This article represents an example of very, very new genetic information on ovarian cancers that in the distant future could lead to new types of treatment strategies."

RNA interference molecules help regulate gene expression. Specifically, they can shut down genes and, as such, may represent an avenue for treatment.

The two enzymes examined in this study, Dicer (so named because it dices up RNA) and Drosha, are involved in two types of RNA interference.

These researchers measured messenger RNA (mRNA) levels of Dicer and Drosha in tissue samples from 111 patients with ovarian cancer, then correlated these findings with information on survival.

About 60 percent of cancer cells had low levels of the Dicer gene, about half had low levels of Drosha, and about 39 percent had low levels of both genes, Sood said. Low levels of either or both genes was associated with poorer survival. The information was verified in an additional group of 132 ovarian cancer patients.

Low Dicer levels also strongly predicted worse survival in lung cancer and breast cancer patients; Drosha had less of an association in these cancers.

So-called "RNA interference therapies" are coming closer to realization, Sood noted.

"This study helped us figure out that those therapies that would require the enzyme Dicer to be present obviously won't be effective in cells with no Dicer whereas [another type of RNA] does not require Dicer for its function," Sood explained. "That may guide therapy in the future."

More information

The U.S. National Cancer Institute has more on ovarian cancer.



SOURCES: Anil K. Sood, M.D., professor, gynecologic oncology and cancer biology, University of Texas M.D. Anderson Cancer Center, Houston; Robert A. Burger, M.D., gynecologic oncologist and co-director, Ovarian Cancer Research Program, Fox Chase Cancer Center, Philadelphia; Dec. 18, 2008, New England Journal of Medicine


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