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Discovery at Fox Chase Cancer Center May Lead to Future Treatment of AIDS

PHILADELPHIA (April 21, 1999) -- Researchers at Fox Chase Cancer Center have announced an exciting new discovery of importance to AIDS research. The finding suggests that a cellular enzyme may be used as a target for the development of drugs that would block the infection of HIV. The discovery was published in the April 23, 1999 issue of "Science."

Retroviruses, including the virus that causes AIDS, take over normal cell machinery after joining their DNA with the DNA of infected host cells. This irreversible joining of the viral and host genes is essential for the growth of the virus.

In their studies, Fox Chase researchers Rene Daniel, Ph.D., Richard Katz, Ph.D., and Anna Marie Skalka, Ph.D., have found that a known cellular enzyme called DNA-PK, is needed to join the viral and cell DNAs. This enzyme is used by the cell to repair damage to its DNA. The Fox Chase investigators found that the ability of the virus to infect cells is reduced substantially if this enzyme is missing.

"This result suggests that by blocking the ability of the virus to use this enzyme, or others in the cell's DNA repair pathway, we may be able to inhibit the replication of the AIDS virus," said Dr. Skalka. "But much more work is needed to determine if this is a useful strategy. Because design and screening of drugs that target DNA-PK remain to be done, use of this approach as a therapy for HIV infection is several years away."

Current therapies for AIDS target HIV enzymes with a cocktail of drugs aimed at inhibiting several processes critical to virus survival. These processes include the synthesis of viral DNA and alteration of the virus's protein core.

However, HIV is capable of mutating readily and its enzymes often become resistant to the drugs in use. The current use of a therapeutic cocktail of several drugs is pinned on the hope that the virus will not become resistant to all the drugs at once and will still be killed by at least one of the components of the cocktail.

"The great advantage to targeting a cellular enzyme like DNA-PK is the very low probability that the virus will develop drug resistance," added Skalka.

The research by Drs. Skalka, Daniel and Katz stemmed from work involving retroviruses that cause cancer.

Fox Chase Cancer Center is one of 35 National Cancer Institute-designated comprehensive cancer centers in the nation. The Center's activities include basic and clinical research, prevention, detection and treatment of cancer and community outreach programs.

Fox Chase Cancer Center, part of the Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence four consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach.  For more information, call 1-888-FOX CHASE or (1-888-369-2427).

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