Researchers identify deadly “fake signal” in breast cancer

SAN ANTONIO (December 13, 2010) — Researchers have identified a false signal produced by the body that, by pretending to be estrogen, outwits hormonal therapies that fight breast cancer.

The discovery may lead to new therapies using existing drugs to fight tumors that have become resistant to hormone therapy, said Tyler Curiel, M.D., M.P.H., an immunologist at the Cancer Therapy & Research Center at the UT Health Science Center San Antonio who co-authored the study, which was published this month in the journal Cancer Research.

Most breast cancers start off being sensitive to estrogen, which can stimulate the growth of certain tumors, Dr. Curiel said, and in that state, they’re relatively easy to treat with anti-estrogen agents.

However, “we know that when women lose their estrogen receptor, that signals a worse prognosis,” Dr. Curiel said. “The big questions have always been: if the estrogen receptor is gone, why is the cancer still growing? Why has it become resistant to hormone therapy? And how does it metastasize?”

What the researchers discovered was that at that point the cancer is not fueled by estrogen — it’s fueled by a fake signal. And they have identified a protein in the body that gives that signal.

The protein is called CXCL12. It sends a signal to a receptor, CXCR4, that makes the cell respond like it is getting estrogen when it is not. Hormonal therapies block estrogen signaling – but hormonal agents can’t block CXCL12, because it’s not estrogen. So this signal allows even tumors that no longer have the estrogen receptor to keep growing.

“We’re looking at how one molecule can control two of the major problems in breast cancer therapy — metastasis and therapeutic resistance,” said fellow researcher Matthew Burow, associate professor of medicine at Tulane University School of Medicine. “Other people have looked individually at CXCR4 and the estrogen receptor.

We’re looking at how the interaction of how these pathways are driving breast cancer to a more aggressive and resistant phenotype.”

Researchers first used a mouse model to identify the process, then examined data that showed that women whose breast cancers had this receptor died a lot sooner than women who didn’t.

“It appears to explain most of the fundamental hallmarks of the kind of breast cancer that kills,” Dr. Curiel said. “There are drugs right now that block that receptor. Also, the receptor does a lot of things in lots of other cancers. So it’s immediately and highly translatable to clinical trials right now.”

The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio is one of the elite academic cancer centers in the country to be named a National Cancer Institute (NCI) Designated Cancer Center, and is one of only four in Texas. A leader in developing new drugs to treat cancer, the CTRC Institute for Drug Development (IDD) conducts one of the largest oncology Phase I clinical drug programs in the world, and participates in development of cancer drugs approved by the U.S. Food & Drug Administration. For more information, visit

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