New inhibitors of breast cancer cells identified

A team of U.S. scientists has identified a new family of compounds that block the ability of estrogen to stimulate the growth of breast cancer cells.

New inhibitors of breast cancer cells identified
"The lead inhibitor is quite effective in breast cancer cells that are resistant to tamoxifen," Dr. David J. Shapiro noted at the Endocrine Society's annual meeting underway in San Francisco.

"We are hopeful that as we proceed with further development that these compounds may ultimately lead to therapeutics that are clinically useful against some breast cancers that are resistant to current therapies," added Shapiro, a biochemist at the University of Illinois at Urbana-Champaign.

Currently available treatment for breast cancer driven by estrogen either interfere with estrogen production (e.g., aromatase inhibitors such as letrozole) or block estrogen's ability to bind to estrogen receptors on breast cancer cells (e.g., tamoxifen).

"We targeted a different step in the pathway of estrogen action," Shapiro said, "one that is not targeted by current therapeutics" -- namely, the expression of genes within cell that are controlled by estrogen receptor activity and that contribute to cancer growth.

The researchers found that a compound called TPBM blocked the estrogen-dependent growth of human breast cancer cells that carried estrogen receptors -- even cells resistant to tamoxifen treatment. If cells did not carry estrogen receptors (i.e., ER negative), they were not affected.

"Even at very high concentrations, TPBM has no effect on ER-negative cells, so it is not toxic to these cells at all," Shapiro said. "This gives us a lot of confidence as we go to animal studies that TPBM will not damage human cells."

He noted that while tamoxifen therapy is effective initially, "in essentially all patients, the tumors eventually become resistant to tamoxifen and resume their growth." This fact "underscores the importance of identifying new classes of therapeutic agents that will act outside of the hormone-binding pocket on the estrogen receptor."


Reuters
Last Mod: 18 Haziran 2008, 15:45
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