Estrogen receptor coregulator binding modulators (ERXs) effectively target estrogen receptor positive human breast cancers

Around 70% of breast cancers in women need one or both of the female hormones (estrogen and progesterone) to grow. To treat these 'hormone-dependent' cancers, patients receive drugs that either block the production of estrogen or directly target a receptor protein that senses estrogen in the cancer cells. Unfortunately, many breast cancers develop resistance to these drugs. This resistance is often caused by genetic mutations that alter the estrogen receptor; for example, the receptor may develop the ability to interact with other proteins in the cell known as coregulators to promote tumor growth. Developing new drugs that prevent estrogen receptors from interacting with coregulators may provide more options for treating hormone-dependent breast cancers. Here, Raj et al. developed a new small molecule named ERX-11 that is able to inhibit the growth of human breast cancer cells that are sensitive to existing drugs as well as cells that have become drug-resistant. For the experiments, hormone-dependent breast cancer cells from humans were transplanted into mice. This procedure usually causes the mice to develop tumors, but giving the mice ERX-11 by mouth stopped estrogen receptors from interacting with coregulators and blocked the growth of tumors. Furthermore, ERX-11 does not appear to have any toxic effects on the mice, indicating that it may also be safe for humans. The findings of Raj et al. suggest that ERX-11 is a promising new drug candidate for treating some breast cancers. The next steps are to examine the effects of ERX-11 on mice and other animals in more detail before deciding whether this molecule is suitable for clinical trials. In the longer term, molecules similar to ERX-11 could also be developed into drugs to treat other types of cancer that are also caused by abnormal interactions of coregulator proteins.