New Molecular Target Discovered in Estrogen Receptors for Breast Cancer Treatment

Current Breast Cancer Therapies

Researchers have identified a previously unknown molecular target within estrogen receptors, paving the way for innovative breast cancer drug development. Existing treatments primarily focus on blocking estrogen receptors, which can slow the progression of breast cancer. However, rapid mutations in tumor cells often lead to resistance against these receptor-blocking medications, highlighting the need for more treatment options.

Breakthrough Research at Case Western Reserve University

A team from Case Western Reserve University in Ohio has made significant strides by uncovering a new structure within the estrogen receptor that can potentially be targeted to disrupt its activation. While previous studies have detailed the structure of individual receptor components, the interactions between these subunits remained unclear until now.

Mapping the Estrogen Receptor Structure

The researchers successfully mapped the complete structure of the estrogen receptor for the first time, utilizing a combination of small-angle X-ray scattering and computational modeling techniques. Their findings, published in Nature Communications, reveal a bridge-like structure that connects the receptor’s two critical parts—those that bind to estrogen and DNA.

Impact of the New Structure

The study indicates that obstructing this interface can effectively hinder communication between the receptor’s two essential subunits, thereby disrupting the signaling pathway involved in breast cancer progression. The team developed fluorescent probes to monitor the normal functioning of this structure and identify when disruptions occur.

Future Directions in Drug Development

Plans are underway for large-scale screening of existing drugs to identify those capable of effectively interfering with this signaling pathway. By repurposing already available medications for breast cancer treatment, researchers aim to expedite the lengthy drug development process.

Reference

Huang W et al. Multidomain architecture of estrogen receptor reveals interfacial cross-talk between its DNA-binding and ligand-binding domains. Nat Commun. 2018 Aug 30;9(1):3520. doi: 10.1038/s41467-018-06034-2.

Author

Written by Agustin Dominguez Iino, BSc.