Chemotherapy, one of the standard treatments for prostate cancer, works in part by targeting receptors on cancer cells. But these cells can adapt in the face of chemo, and become resistant to the drugs, limiting their effectiveness. Scientists at the University of Missouri have risen to the challenge, drafting a compound that was originally designed to fight cholesterol into the war on prostate cancer.
"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," said Salman Hyder, professor of biomedical sciences in the MU College of Veterinary Medicine and the Dalton Cardiovascular Research Center. "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."
Chemotherapeutic drugs target androgen receptors inside the prostate cancer cells. These receptors in turn bind with testosterone and other hormones. Often anti-hormone therapies, or chemical castration, is used to target prostate cancer.
"Although tumor cells may initially respond to these therapies, most eventually develop resistance that causes prostate cancer cells to grow and spread," Hyder said. "Cholesterol also can contribute to the development of anti-hormone resistance because cholesterol is converted into hormones in tumor cells; therefore, these cholesterol-forming pathways are attractive therapeutic targets for the treatment of prostate cancer."
Hyder and his colleagues used a cholesterol-reducing compound called RO 48-8071 to test their theory on human prostate cancer cells. They learned not only that it worked to reduce the growth of the cancerous cells, but in follow-up studies discovered that the molecule actually caused cancer cell death.
Upping their game, they then tested the results in mice with human prostate cancer cells. After injecting the compound into the rodents, the team learned that the molecule was effective in reducing tumor growth.
“These findings suggest that the potential cholesterol drug, when used in combination with commonly used chemotherapeutic drugs, could represent a new therapeutic approach in the fight against prostate cancer,” Hyder said.