New Target for HER2-Positive Breast Cancer

Estrogen related receptor alpha protein can be targeted to halt tumor growth

(RxWiki News) HER2-positive breast cancer is not only aggressive, but it's difficult to eliminate. A recent discovery has found a molecule that could be targeted with new drugs to treat this treacherous form of breast cancer..

Duke Cancer Institute researchers have identified a protein within breast cancer cells that drive aggressive tumor growth in some forms of the disease. Drugs could be developed to target this molecule to slow or block this out-of-control growth.

"HER2-positive breast cancers may soon have new drug therapies."

Most (75 percent) breast cancers are fueled by estrogen and are known as estrogen receptor-positive (ER+). Existing therapies work by blocking estrogen.

The remaining estrogen receptor-negative (ER-) breast cancers - including HER2-positive - are particularly worrisome because they don't respond to current therapies designed for estrogen driven disease. Some existing treatments do interfere with the growth of HER2 cancers, but these tumors often grow resistant, at which point the therapies no longer work.

A research team, led by Donald McDonnell, Ph.D., chairman of the Duke Department of Pharmacology and Cancer Biology, focused on the protein known as estrogen-related receptor alpha (ERRa), which appears to stimulate tumor growth.

After performing genomic analysis to profile 800 breast tumors, researchers found a link between ERRa and aggressive growth in ER- breast cancers. McDonnell reports that when the protein is active, patients do "much, much worse."

Using an investigational drug candidate, researchers were able to actually shut down ERRa in the laboratory, which in turn stopped tumor cells from multiplying.

dailyRx spoke with McDonnell, a Glaxo-Wellcome Professor of Molecular and Cellular Biology (MCB) and asked him when a drug is likely to become available. "The compounds we used in our study are first generation inhibitors that are unlikely to be developed in and of themselves," he said.

"However, several companies have developed second generation inhibitors with improved drug properties that are progressing towards the clinic. I think that the results of our study will be instructive to these drug developers as to the types of patients (tumor characteristics) that are most likely to respond to this class of inhibitor," McDonnell said.

ERRa is active in different malignancies. As a result, in addition to breast cancer, the drug being developed could also be used to treat colon, ovarian and other cancers.

McDonnell's research team is currently investigating why ERRa contributes to aggressive breast cancer. The researchers are also working on developing a drug to block the activity of this protein.

Findings of this study are published in the October 18, 2011, print issue of the journal Cancer Cell.

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Review Date: 
October 17, 2011