Targeting androgen receptors may reduce tumor size in some breast cancers

A cancer radiotherapy room. A new study has identified a potential drug target for breast cancer. File Photo by polat/Shutterstock
A cancer radiotherapy room. A new study has identified a potential drug target for breast cancer. File Photo by polat/Shutterstock

March 31 (UPI) -- The male reproductive hormone androgen may hold the key to a new treatment approach for estrogen receptor-positive breast cancer, the most common form of the disease, a new study has found.

Researchers found that by activating the proteins in cells to which testosterone and androgen bind -- androgen receptors -- using the drug enobosarm they were able to reduce tumor growth in breast cancer tissues, according to an analysis published in a special supplemental section of the Journal of the Endocrine Society.


Approximately 75 percent of all breast cancer cases worldwide involve the estrogen receptor-positive type. New drug treatments are needed because as many as 35 percent of women eventually become resistant to currently available hormone therapies, researchers say.

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"There is a prevailing assumption that the androgen receptor promotes malignancy in breast cancer, as it does in prostate cancer," study co-author Dr. Wayne Tilley, a professor at the University of Adelaide in Australia, said in a press release. "Our study demonstrates that this is not the case for ER-driven breast cancer. Rather, the androgen receptor acts as a tumor suppressor."

Androgen receptors are proteins in cells to which testosterone and other "male" reproductive hormones bind to elicit their effects. Androgens are found in women as well as men, according to Tilley, who added that androgen receptor-stimulating drugs are under investigation for various diseases, including breast cancer.


He and his colleagues tested one of these drugs, enobosarm, a selective androgen receptor modulator, or SARM, in models of estrogen receptor-positive breast cancer, using cell lines that are commercially available, as well as tissues taken from breast cancer patients, including those resistant to current therapies.

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Some cell lines and human tissues were grown in the lab, while others and patient tumors were transplanted into mice to create models for the study.

In general, researchers found evidence that stimulating androgen receptor activity with enobosarm stopped tumor growth. From the breast cancer models, they derived a gene "signature" of androgen receptor activity that predicted cancer survival in participants in large studies of ER+ breast cancer, and it outperformed other breast cancer prognostic signatures, Tilley noted.

When the investigators treated estrogen receptor-positive breast cancer tissues with enobosarm combined with breast cancer drugs such as tamoxifen that target the estrogen receptor, Tilley said they observed better reduction in tumor growth than with tamoxifen alone.

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"Treatment of ER+ breast cancer with an androgen receptor activator drug could be immediately tested in women," Tilley said.

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