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Thursday, November 27, 2014

Cholesterol-lowering drug found effective for breast cancer treatment

Cholesterol and hormone therapy could be the key to fighting cancer with minimal side effects, MU research team finds.

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Ben Kothe/Graphic Designer

July 8, 2014

A revolutionary cholesterol-lowering cancer treatment has yielded promising results after being tested extensively on breast cancer tumors by MU researchers.

The researchers discovered the cholesterol-lowering drug, RO 48-8071, killed tumor cells by following a gut instinct. Cancer cells need cholesterol to multiply and some breast cancer treatments raise cholesterol levels, so they hoped lowering cholesterol would help treat cancer.

Salman Hyder, professor of biomedical sciences, said he and fellow researchers were surprised when they found the drug was killing tumor cells.

“‘Why is it killing tumor cells?’” Hyder said. “Not only does it shut down cholesterol, but what else is it doing?”

Two different types of testing were performed using the drug. The drug was first tested on individual human breast cancer cells outside of the body, in vitro. In addition, human breast cancer cells were injected into mice, where they could continue to grow. The treatment was then used on the mice to treat the cancer.

Through these tests, the MU researchers discovered the drug was destroying one of the major proteins involved with the estrogen receptors. This is significant because hormone-dependent breast cancer tumors require estrogen receptors to grow.

“This drug not only lowers cholesterol, but it destroys one major protein in breast cancer that is required for proliferation, for cells to grow,” Hyder said.

However, the team has not begun testing the drug in patients with breast cancer yet.

According to Yayun Liang, associate research professor of biomedical sciences, the drug works for hormone-dependent breast cancer, which around 70 percent of all women with breast cancer have.

“We have not tested extensively (with) other cancers, but the indications are that (the drug) does affect other cancers,” Hyder said. “But we are concentrating on breast cancer at this time.”

Chemotherapy is problematic due to the negative side effects, which range from losing hair to weakening the immune system. The researchers’ goal is to combine the new drug with chemotherapy to reduce the concentration of the chemotherapy, making it less toxic.

“This is our aim: to see if we can combine (the new drug) with other commonly used chemotherapeutic drugs and see if we can lower the concentration, so that they can be taken easily by patients,” Hyder said.

Additionally, the cholesterol-lowering drug was found to cause no levels of toxicity in the mice, but it is unclear if side effects will affect patients taking the drug.

“We don’t know how this will actually behave when it’s inside the human body,” Hyder said. “So that is why we need the phase one trial, which is actually done for safety reasons, with very low concentrations of this drug.”

Phase one trials are just one step on a long path to Food and Drug Administration (FDA) approval. Hyder estimated the drug would take around eight to ten years to reach patients, if it is approved at all.

The drug needs the backing of doctors willing to do clinical trials to continue. However, Hyder said he has high hopes for the drug.

“Our hope is that once we continue this for a long time it will lead to a cure, but we cannot say that definitively at this time,” Hyder said.

In the meantime, their finding that higher cholesterol leads to an increase in cancer-causing hormones suggests changes in diet can help lower the risk of cancer and may aid chemotherapy treatments.

“All the evidence now suggests that people who have lower cholesterol levels have a lower risk of cancer,” Hyder said.

In the future, cholesterol-based research could lead to a method of lowering the risk of cancer in high-risk patients and offer a less toxic treatment for those affected by cancer.

“If we can get a significant amount of funding, we will definitely test (prevention),” Liang said. “This also can be a project for graduate students to work on.”

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