Posted on July 30, 1999 03:34 PM PDT

WESTPORT, Jul 30 (Reuters Health) - Data reported in the July 30th issue of Science may help researchers find ways of preventing tamoxifen resistance.

Using genomic-based drug discovery techniques, researchers at Duke University Medical Center and Novalon Pharmaceutical Corp., both in Durham, North Carolina, tested billions of peptides to determine how they interact with estrogen receptor alpha in the presence of various drugs.

"What we found were peptides that were common to both estrogen and tamoxifen, and peptides that were unique to each," study director Dr. Donald P. McDonnell of Duke said in a university statement.

The finding of peptides that function as ligand-specific receptor antagonists indicates "...that estradiol-agonist and tamoxifen-partial agonist activities do not occur by the same mechanism," the researchers write.

"This told us that...tumors which are resistant to tamoxifen may not be resistant to other [selective estrogen receptor modulators]," Dr. McDonnell said in the Duke statement.

"Basically, what we have found is something that was totally unexpected," he told Reuters Health."Clearly, this is saying that there is a unique property of the tamoxifen-receptor complex."

The finding sheds new light on the unique mechanisms underlying the development of tamoxifen resistance, Dr. McDonnell said.Previously, he explained, researchers believed that tamoxifen resistance developed as a result of the drug's estrogen-mimicking effects.

Dr. McDonnell and colleagues conclude in the journal that "[t]he ability to regulate estrogen receptor alpha transcriptional activity by targeting sites outside of the ligand-binding pocket has implications for the development of estrogen receptor alpha antagonists for the treatment of tamoxifen-refractory breast cancers."

Science 1999;285:744-746.