Some compounds that may inhibit the growth of estrogen-dependent breast cancer cells have been identified by researchers from University of Illinois, Colorado and North Carolina. This may help find new drugs for the treatment of the cancer.
Estrogen plays a key role in the growth of breast cancer. More than 80 percent of breast cancer tumours in women over the age of 45 are activated by estrogen by way of a protein called an estrogen receptor.
The researchers have identified several compounds that can reduce the binding of estrogen-receptor complex to the regulatory regions of genes.
"This cell-based study is exciting because it suggests these compounds are likely to be effective in tumours that remain dependent on estrogen for growth but are resistant to current therapies," said principal investigator David J. Shapiro, a professor of biochemistry in the School of Molecular and Cellular Biology at the University of Illinois.
The present treatments include the use of drugs, such as tamoxifen, that interfere with estrogen's ability to bind to the estrogen receptor.
However, over the time it become resistant to tamoxifen. In some resistant tumours, tamoxifen even begins to act like estrogen and actually stimulates tumour growth.
"Tamoxifen is useful in that it is very effective at blocking recurrence of breast cancer in patients for whom the entire tumour is removed. But for patients who still have existing tumours, eventually those tumours will become resistant," Shapiro added.
Shapiro's team sought to target other steps in the pathway of estrogen action.
Using a technique they developed that can quickly determine whether the target DNA is, or is not, bound by the estrogen-receptor complex, the team was able to screen a long list of potential therapeutic compounds to see if they inhibited the binding of the complex to the DNA. They then tested these agents in ER-positive breast cancer cells.
These agents effectively retarded production of the proteins that promote the growth and proliferation of ER-positive breast cancer cells.
"These small molecules specifically block growth of estrogen-dependent breast cancer cells with little or no effect on other cells. This work sets the stage for further development and testing of these inhibitors," Shapiro said.
The study was presented at a meeting of the Endocrine Society.