A protein in the nucleus of breast cancer cells that helps stimulate the growth of aggressive breast cancer tumors may be an appropriate target for new drug treatments, researchers from the Duke Cancer Institute report. The study was published in the October 18, 2011, issue of the journal Cancer Cell.
“This is validation of a new drug target for a subset of breast cancers that have poor treatment options,” said the study’s senior author, Donald McDonnell, PhD, chairman of the Duke Department of Pharmacology and Cancer Biology.
About 25% of breast cancers are not fueled by estrogen. HER2-positive tumors are among the most prevalent malignancies in this class. For the study, McDonnell and his team focused on a protein inside the nucleus of tumor cells that has a relationship with HER2. This protein, known as estrogen-related receptor alpha (ERRα), controls genes related to energy metabolism.
McDonnell’s team detected a relationship between the protein’s activity and the aggressiveness of estrogen-negative cancers by using a genomic analysis to profile 800 breast tumors.
“When that ERRα receptor is active, the outcome of these patients is much, much worse,” McDonnell said.
Tumor growth appears to escalate after the protein receives a signal from different hormone receptors. Researchers found one specific trigger is HER2, and another is IGF-1R. Therefore, ERRα is active in all breast cancer tumors where either HER2 or IGF-1R is also active.
“There are a lot of proteins that play important roles in breast cancer pathogenesis, but disappointingly, the activity of only a few of these proteins can be inhibited by drugs,” McDonnell said. “In contrast, it’s relatively easy to interfere with ERRα’s function. So instead of looking for the pathways that lead to ERRα activation, we can aim directly at the target ERRα. It doesn’t matter what’s upstream.”
Because ERRα is highly active in many malignancies, McDonnell said the new drug approach could also be applied to colon, ovarian, and other cancers.
“The initial excitement is we have found a target that seems to be important for estrogen-negative cancers,” McDonnell said.
Source: Duke University Medical Center.