The University of Vermont Cancer Center (UVMCC) is proud to share that Frances Carr, PhD, has received a prestigious Discovery Boost Grant from the American Cancer Society, along with co-investigator Seth Frietze, PhD. Both are members of UVMCC’s Cancer Cell research program. This two-year award supports high-risk, high-reward research designed to spark innovation and open new avenues in cancer treatment. 

 Building on prior work by Drs. Carr and Frietze at the UVM Cancer Center, this project— “A Novel Approach to Targeting ESR1 Mutant Breast Cancer with TRβ-Selective Agonism”—addresses a major challenge in breast cancer treatment: resistance to endocrine therapy caused by mutations in the estrogen receptor gene (ESR1). These mutations allow tumors to continue growing even when estrogen signaling is blocked, leaving patients with limited treatment options. 

The study focuses on drugs that activate thyroid hormone receptor beta (TRβ), a member of the nuclear hormone receptor family that has recently been recognized for its tumor-suppressing properties. By examining how TRβ activation affects cancer cells with ESR1 mutations, the research aims to identify the molecular pathways that drive treatment resistance, and to test whether TRβ-targeted therapies can overcome it. Ultimately, this work explores a new therapeutic strategy for patients with advanced, treatment-resistant, estrogen receptor–positive breast cancer.

“Therapy resistance remains one of the greatest challenges in treating ER-positive breast cancer," says Dr. Carr. “Our goal is to uncover how TRβ activation can counteract ESR1 mutations, and restore therapeutic responsiveness. This research could open the door to entirely new strategies for patients with advanced, drug-resistant disease.”