The McDonnell Lab

Using biochemical, genetic, and chemical biological approaches to identify targetable regulatory steps in estrogen, androgen, progesterone, and estrogen-related receptor signaling pathways in cancer

Our Approach

Identify targetable nodes in nuclear receptor signaling pathways that are important in cancer pathobiology and exploit this information to direct mechanism-based approaches to discover new therapeutics and/or instruct the optimal use of existing drugs to treat (or prevent) breast and prostate cancers.

Our Goal

To do translational research that will help to change the conversation from “how to treat” to “how to cure” cancers of the breast and prostate.

Our Translational Successes

Developed the concept of functional receptor allostery and used it to identify etacstil, the first Selective Estrogen Receptor Downregulator (SERD) evaluated as a treatment for metastatic breast cancer.

Defined the utility of Elacestrant, a SERD, as a treatment for ER-positive breast cancer (IP licensed to Radius Health, FDA approved January 2023; EC approved September 2023).

Repurposed lasofoxifene as a therapeutic for patients whose breast tumors express activating mutations in the estrogen receptor (IP licensed to Sermonix, In Phase III ELAINE trials).