Breast cancer drug gets boost

Natural protein could make the most aggressive breast cancers vulnerable tamoxifen, and may even prevent the cancer’s spread

EDITOR’S NOTE: On December 2, 2010, the Proceedings of the National Academy of Sciences published a retraction online of the research article discussed in this story. The full text of the retraction is available here.

Scientists have found a way to make cancer drugs work against drug-resistant types of breast cancer. The new research could provide another treatment option to women with particularly aggressive breast cancers, the scientists report online February 23 in Proceedings of the National Academy of Sciences.

Most breast cancers produce proteins called hormone receptors. Cancer drugs like tamoxifen work well against these cancers because tamoxifen binds to the hormone receptors and kills the cancer cell.

But about a third of breast cancers don’t make hormone receptors — so drugs like tamoxifen don’t have a target. These types of breast cancer, called hormone receptor–negative breast cancer, are more aggressive than other cancers and more likely to spread to other organs. Because drugs that target hormone receptors won’t work, treatment options are limited to chemotherapy. “There’s just less in our arsenal to fight hormone receptor–negative cancers,” comments Paula Vertino, cancer biologist at the Winship Cancer Institute at Emory University in Atlanta.

In the new work, a special protein induced hormone receptor–negative breast cancer cells in the lab to produce the receptors and respond to tamoxifen treatment, cancer biologist Caroline Ford of Lund University in Malmö, Sweden, and her colleagues found.

As well as kick-starting hormone receptor production in breast cancer tumors, Wnt-5a can help prevent cancer from spreading. In mice treated with Wnt-5a, the breast cancer was 70 percent less likely to spread to the liver or lungs. The protein seems to make cancer cells stick together, preventing them from migrating to other organs, Ford says.

After noticing that breast cancer cells without the receptors had low levels of the protein, called Wnt-5a, the team hypothesized that Wnt-5a levels were linked to production of the receptors. Adding Wnt-5a protein to the lab dishes activated the gene for producing the receptors. This gene remains intact even in cells that become cancerous, Ford says.

Wnt-5a is a member of a large family of Wnt proteins. “Maybe different Wnt proteins could be used for different types of cancer,” Ford speculates. Nonetheless, Wnt-5a has already been linked to other cancers, including colon cancer, thyroid cancer and lymphoma.

Previous studies have identified other ways of making breast cancer cells produce hormone receptors, but concerned about toxicity and side effects had remained, Ford says. Because Wnt-5a is already found in cells naturally, it shouldn’t carry any ill effects.

Still, the researchers were worried that Wnt-5a would be too large and unwieldy to move easily into cells in a person’s body, so the team developed a smaller protein that has similar properties, named Foxy-5. But, “we don’t know a lot about how Foxy-5 would work as a treatment,” Vertino comments. Before use of a combination of Foxy-5 and tamoxifen becomes widespread, the researchers need to check that the two drugs work well together in organisms, not just in cells.

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