Turning Off Breast Cancer

Understanding Estrogen Receptor Cross-Talk

By Jill Burke

Communication is essential to life — it may also hold the key to understanding what signals breast cancer growth. By studying how hormonal and environmental agents interact with the estrogen receptor, researchers hope to find a new class of antiestrogen drugs to stop breast cancer in its tracks.

“Our basic research involves understanding how the estrogen receptor, which binds estrogenic steroid hormones, regulates expression of genes and the growth of tumors in breast cancer cells,” says Dr. Stephen Safe, a world-renowned researcher who holds the title of Distinguished Professor at Texas A&M University’s College of Veterinary Medicine and Biomedical Sciences and in the Institute of Biosciences and Technology in The Texas A&M University System Health Science Center.

Safe and his research associates are looking closely at the role receptors play in the development of breast cancer. The formation of breast tumors is a complicated process, Safe says, and various compounds can activate or deactivate pathways that lead to cancer. “Cancer is not simple. It’s a process where you start out with some initial cell damage that escapes all sorts of surveillance and eventually leads to an altered cell,” explains Safe. “The process continues until you finally get a tumor. So, we’re looking at how and why receptors activate and shut off the pathways that lead to tumor formation.”

Endocrine disruptors, estrogenic compounds in the environment and in plants that people eat, are also being studied. “We’re interested in how these compounds activate estrogen receptor signaling in breast cancer cells,” says Safe. “Comparing environmental estrogens’ signaling process versus how the natural female hormone estradiol does it,” says Safe, “will help us determine if synthetic estrogens might be a risk factor for breast cancer or how they might protect us from breast cancer.”

Safe is also studying how environmental chemicals and drugs activate a particular molecule called the Ah, or aryl hydrocarbon, receptor and how the Ah receptor turns off estrogen receptor signaling. “We’re trying to understand this inhibitory Ah receptor–estrogen receptor cross-talk in breast cancer cells and other estrogen-responsive tissues,” says Safe.

“Through understanding how the Ah receptor shuts off estrogen receptor signaling, which causes breast cancer cells to change and multiply, we can potentially design nontoxic selective compounds that block the growth of breast cancer,” explains Safe. “By turning off estrogen receptor–dependent responses, we can develop new anticancer drugs.”

Safe’s research endeavors, funded primarily by the National Institutes of Health, have added to the understanding of what genes are involved in the spread of breast cancer. “We have certainly learned a lot in terms of this cross-talk project,” he says. “As a result, we have patented and licensed compounds that target those specific genes. Our next steps include further development of these compounds, marketing them to pharmaceutical companies and then getting them in the hands of clinicians. It’s a long and arduous process.”

Designing drugs that act differently and may be useful alone or in combination with another drug is Safe’s research goal. “For a new drug to be accepted, it has to be either better, or the combined treatment has to offer advantages,” according to Safe. “We think our new drug offers advantages not currently available.”