Cancer and Cholesterol

A re-purposed drug offers a new approach to treating a common killer.

When prostate cancer kills, it typically does so after becoming resistant to chemotherapy drugs targeting cancer cells’ androgen receptors. As the disease progresses into later stages, these cells can also become resistant to chemical-castration therapies. More than half of patients with “castration-resistant prostate cancer” will experience metastasis to bone. At this point death becomes inevitable.

MU’s Salman Hyder, professor of biomedical sciences and Zalk Endowed Professor in Tumor Angiogenesis, is working on disrupting this discouraging cycle of chemotherapy and resistance. In a study recently published in the journal OncoTargets and Therapy, Hyder and his laboratory team at the Dalton Cardiovascular Research Center discovered that an existing treatment for high cholesterol — one that never made it to market — was lethal to human prostate cancer cells.

“Cholesterol is a molecule found in animal cells that serves as a structural component of cell membranes. When tumor cells grow, they synthesize more cholesterol,” says Hyder. “Often, cancer patients are treated with toxic chemotherapies; however, in our study, we focused on reducing the production of cholesterol in cancer cells, which could kill cancer cells and reduce the need for toxic chemotherapy.”

During the study, Hyder and his team administered an anti-cholesterol compound developed by Roche Pharmaceuticals to human prostate cancer cells. They found it was effective in reducing prostate cancer cell growth. Subsequent studies determined that it also killed cancer cells.

The researchers next tested the compound in mice with human prostate cancer cells. It was again effective in reducing tumor growth.

These findings, Hyder says, offer hope that a cholesterol drug, when used in combination with commonly used chemotherapeutic agents, might represent an important new therapeutic approach against prostate cancer.

Millions could benefit. According to the World Health Organization, prostate cancer is the third leading cancer-related cause of death among men in developed countries. In the U.S., according to the NIH’s National Cancer Institute, some 180,000 American men will be diagnosed with prostate cancer this year. An estimated 26,000 will die from the illness.

Scientists involved with the study included Yayun Liang, a research associate professor at MU and Benford Mafuvadze, a former MU post-doctoral fellow, and Johannes Aebi from Roche Pharmaceuticals.

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