Crystallography Confirms Drug-Protein Interaction that May Prevent Certain Breast Cancers


Scientists used X-ray macromolecular crystallography at the Advanced Photon Source (APS), a U.S. Department of Energy Office (DOE) of Science User Facility at the DOE’s Argonne National Laboratory, to determine the structures of estrogen receptors on breast cancer cells in mice and the drug lasofoxifene, confirming that lasofoxifene binds to the receptors.

The APS uses ultrabright X-rays to illuminate the structures of proteins like estrogen receptors, often looking to see if drug compounds attach themselves to these proteins. Structures were determined at the Structural Biology Center (SBC) and at the South-East Regional Collaborative Access Team beamlines.

About 75% of breast cancers are estrogen receptor positive, meaning that the hormone feeds tumor growth. Treatment with lasofoxifene outperformed fulvestrant, the current gold-standard drug, in reducing or preventing primary breast cancer tumor growth in the mice. The drug also was more effective at preventing metastasis to the lung, liver, bone, and brain — the four most common areas for breast cancer to spread. Human clinical trials are underway.

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Muriel Lainé, Sean W. Fanning, Ya-Fang Chang, Bradley Green, Marianne E. Greene, Barry Komm, Justyna D. Kurleto, Linda Phung, Geoffrey L. Greene, “Lasofoxifene as a potential treatment for therapy-resistant ER-positive metastatic breast cancer,” Breast Cancer Res. 23, 54 (2021). [DOI: 10.1186/s13058-021-01431-w]