First-in-class molecule offers new hope for recalcitrant ER-positive breast cancers

By Liz Meszaros, MDLinx
Published August 11, 2017

Key Takeaways

Researchers have discovered a first-in-class molecule—ERX-11—that may prevent the growth of estrogen-positive breast cancer in women for whom traditional therapies have stopped working. They published their results in the journal eLife.

“This is a fundamentally different, new class of agents for estrogen-receptor-positive breast cancer,” said Ganesh Raj, MD, PhD, professor, urology and pharmacology, UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center, Dallas, TX. “Its unique mechanism of action overcomes the limitations of current therapies.”

Approximately 80% of breast cancers are estrogen-sensitive, and can be successfully treated with hormone therapy with agents including tamoxifen. Unfortunately, as many as one-third of these cancers can eventually become treatment resistant.

Tamoxifen binds to the estrogen receptor in cancer cells, and prevents estrogen from binding to the receptor, a step that is necessary for cancer cells to multiply. Over time, however, the estrogen receptor may mutate, changing its shape, and thereby making it impossible for the treatment drug to continue to "fit" with the receptor. Once this occurs, the cancer cells can start multiplying again.

“There has been intense interest in developing drugs that block the ability of the estrogen receptor – the prime target in most breast cancers – from interacting with the co-regulator proteins that cause a tumor’s growth. Blocking such ‘protein-protein interactions’ has been a dream of cancer researchers for decades. Dr. Raj and his colleagues have done the remarkable by discovering what could be the first-in-class of a therapeutic that realizes this dream,” said David Mangelsdorf, PhD, professor and chairman, department of pharmacology, who holds the Alfred G. Gilman Distinguished Chair in Pharmacology, and the Raymond and Ellen Willie Distinguished Chair in Molecular Neuropharmacology in Honor of Harold B. Crasilneck, PhD.

ERX-11 mimics a peptide, has been tested in mice and ex vivo studies, and has proven to work well, with no signs of toxicity. ERX-11 also offers an advantage in that it is an oral rather than intravenous medication. According to Dr. Raj, clinical trials will be underway in about 1 year.

“This could be a first-line breast cancer therapy down the line. It could even lead to new treatments for other hormone-sensitive cancers. For now, it offers hope for women with estrogen-sensitive breast cancer for whom conventional therapies fail,” Dr. Raj concluded.

Funding for the research was provided by the National Institutes of Health, the Cancer Prevention and Research Institute of Texas, Department of Defense, Congressionally Directed Medical Research Programs, the Welch Foundation, and the Mimi and John Cole Foundation.

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