Novel compounds target dual enzymes to combat hormone-resistant breast cancer

Researchers have found new compounds that could be used to treat a common breast cancer that can be resistant to hormone therapies.

Published in the journal RSC Medicinal Chemistry, new research targets two critical enzymes involved in the production of the hormone estrogen —aromatase and steroid sulfatase—at the same time.

Estrogen receptor-positive (ER+) breast cancer, which makes up around 70% of all breast cancer cases, often becomes resistant to current hormone therapies. Now, researchers have designed and synthesized new compounds that target the two enzymes.

The new potential therapy is called a dual aromatase-steroid sulfatase inhibitor (DASI). Some of these new compounds were found to effectively block both enzymes, which may help reduce estrogen levels in cancer cells more comprehensively.

Dr. Paul Foster from the University of Birmingham and a co-author of the study said, “This is an exciting new development that could pave the way for treating the most common breast cancer when other therapies stop working.

“We have shown for the first time that the particular molecules, called benzofuran-based molecules, act to inhibit the two enzymes, and in doing so find an alternative way to suppress estrogen production and reduce tumor growth.”

Chemical modifications

Previous research involving earlier versions of the compounds only inhibited one enzyme or the other. Achieving dual activity by adding a simple methyl group was an unexpected but crucial insight, showing that small chemical modifications can significantly enhance biological activity.

If developed further, these compounds could offer new treatment options for patients with ER+ breast cancer that has become resistant to standard hormone therapies.

Research collaborators Dr. Claire Simons, University of Cardiff, and Dr. Paul Foster, University of Birmingham hope the findings will lead to the development of a new class of breast cancer treatments.

Further preclinical and clinical studies could explore their use in overcoming resistance to current endocrine therapies. Researchers at both universities are already in the process of developing even more potent dual inhibitors to circumnavigate treatment resistance in ER+ breast cancer.