Researchers have discovered how a drug aimed at controlling the AIDS virus also can destroy a rare form of cancer. The findings, which appeared in the April 1 issue of Clinical Cancer Research, may lead to the drug’s use for other cancers, as well.

Warren Chow (Photo by p.cunningham)

City of Hope researchers led by Warren Chow, M.D., associate professor in the departments of Medical Oncology & Therapeutics Research and Molecular Pharmacology, studied a drug called nelfinavir and its effect on liposarcoma cells. Liposarcoma is a rare form of cancer stemming from fat cells.

Nelfinavir, marketed under the trade name Viracept, was developed to treat HIV, the virus that causes AIDS. It blocks the action of enzymes called proteases, which are crucial for HIV growth and spread.

Scientists have known that protease inhibitors such as nelfinavir have anticancer activity, and in previous research, Chow and his team showed that nelfinavir could kill liposarcoma cells, but exactly how it killed tumor cells was unclear.

In the current study, the City of Hope researchers found that nelfinavir blocks a protein called site-2 protease, or S2P, leading to a build-up of key proteins in the liposarcoma cells. The build-up of those proteins, which are overproduced by liposarcoma cells, causes a cascade of events that drive the tumor cells to kill themselves in a form of programmed cell death called apoptosis.

“The build-up of these fat-cell proteins stresses the liposarcoma cells until they can’t cope, and they basically commit suicide,” Chow said.

The study is the first to show the mechanism behind nelfinavir’s effect on liposarcoma tumor cells, he added.

Chow currently is conducting a clinical trial to test if nelfinavir is safe and effective for liposarcoma patients.

“Now that we understand more about the drug’s mode of action, we can look for other drugs that target S2P or enhance nelfinavir’s effect, as well,” he said.

The team also is looking at nelfinavir’s potential for treating other cancers. Min Guan, M.D., Ph.D., staff scientist in the Department of Molecular Pharmacology, reported promising results of the drug’s effects on hormone-resistant prostate cancer cells, which can develop molecular characteristics of fat cells, at the American Association for Cancer Research’s annual meeting in early April. Guan is first author on the Clinical Cancer Research study, as well.

Other study authors were City of Hope’s Kristen Fousek, Chunling Jiang, Song Guo, Tim Synold, Pharm.D., Bixin Xi and Chu-Chih Shih, Ph.D.