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AIDS Drugs May Fight Cancer, Too

NEW YORK (Reuters Health) - Protease inhibitors, the powerful drugs that fight HIV (news - web sites), the virus that causes AIDS (news - web sites), also seem to block the abnormal growth of blood vessels, Italian researchers report.

Besides helping to explain why people taking protease inhibitors are not as likely to develop a type of cancer that frequently accompanies HIV infection, the finding suggests that the drugs may be beneficial to people with other forms of cancer, researchers say.

(image from CNN)

Kaposi's sarcoma (KS) results in vascular tumors in the tissues under the skin and in mucous membranes, such as the inside of the mouth. Red or purple lesions develop on the skin, as well as on other parts of the body, including the lungs, intestinal tract and lymph nodes. The cancer is thought to be caused by human herpesvirus 8 (HHV-8).

Before the introduction of protease inhibitors during the mid-1990s, KS was common among people who had HIV. But people taking a combination of drugs including at least one protease inhibitor seem to be less likely to develop KS.

Protease inhibitors act on protein-chopping enzymes called proteases, but proteases are not limited to HIV. They also are involved in tumor growth, inflammation and angiogenesis--the formation of new blood vessels.

Dr. Barbara Ensoli, of the Istituto Superiore di Sanita in Rome, and colleagues had a hunch that protease inhibitors might have a direct effect on KS or on the angiogenesis on which the cancer depends.

Ensoli and her colleagues tested two protease inhibitors, indinavir and saquinavir, in mice with KS. Though the mice were not infected with HIV or HHV8, the anti-HIV drugs prevented KS lesions from developing and caused existing lesions to regress, the researchers report in the March issue of the journal Nature Medicine.

Treatment with protease inhibitors also blocked the growth of new blood vessels in mice, the authors note. In fact, the anti-angiogenic effects of protease inhibitors were comparable to paclitaxel, a commonly used chemotherapy drug.

The research indicates that protease inhibitors have powerful effects on angiogenesis, as well as on tumors, Ensoli told Reuters Health. The drugs not only target HIV's protease enzymes, but also cell proteases that are necessary for angiogenesis and the invasion of tumor cells, she explained.

Since tumor growth depends on newly-formed blood vessels to supply blood, blocking angiogenesis and tumor cell invasion with protease inhibitors acts "in a synergistic way to inhibit tumor development or to induce tumor regression," according to the Italian researcher.

Ensoli advised that protease inhibitors be included in the treatment regimen of HIV-positive people who are at risk of tumors, particularly KS. But the findings suggest that the drugs may provide benefits to people who are not infected with the AIDS virus but who have tumors or other diseases marked by too much angiogenesis, she said.

Though protease inhibitors can cause a variety of side effects, the drugs tend to be less toxic than most anti-tumor drugs, Ensoli said. And since the drugs are already widely used, there is no need for additional safety tests, she said.

The next step, she said, is to conduct studies to test the effects of protease inhibitors on KS and other tumors. Ensoli and her colleagues are starting a clinical trial to test the effects of protease inhibitors in HIV-negative people with KS.

"I believe the future research on the anti-angiogenic and anti-tumor effects of protease inhibitors will provide physicians with new drugs, and at the same time will disclose to scientists important clues on the mechanisms of both angiogenesis and tumor growth," she said.

SOURCE: Nature Medicine 2002;8:225-232.