Date of Completion
2024
Document Type
Honors College Thesis
Department
Biochemistry
Thesis Type
Honors College, College of Arts and Science Honors
First Advisor
Frances Carr
Second Advisor
Matthias Brewer
Third Advisor
Jay Silveira
Keywords
thyroid hormone receptor beta, breast cancer, tamoxifen
Abstract
In 2020, the most frequently diagnosed cancer was female breast cancer, with 2.3 million new diagnoses, and amounted to 11.7% of all cancer cases. While therapies that target ERa are common, these therapies often fail due to the development of resistance and subsequent relapse. 40% of patients who use tamoxifen develop resistance and relapse. Therefore, there is a need for novel combinatorial drugs that can reduce tumor growth and delay or prevent the development of resistance. One emergent candidate is another nuclear receptor. Thyroid hormone receptor beta (TRβ) has been shown to be a tumor suppressor in numerous solid tumors. Previous Carr lab data demonstrates selective activation of TRβ using Sobetirome (GC-1), a synthetic thyroid hormone selective for TRβ, reduces estrogen receptor-positive/HER2 negative (ER+/HER2-) cell growth and cancer stem cell formation and increases the efficacy of tamoxifen. Considering estradiol (E2) concentrations are increased in ER+ tumors compared to normal tissues, it is crucial to evaluate treatments in the presence of estrogen to correspond to biological levels. We have continued previous work done in the Carr lab in the presence of E2 to report for the first time that GC-1 reduces malignant phenotype in the presence of estrogen in both MCF7 and tamoxifen-resistant MCF7 breast cancer cells. These findings show the potential of GC-1 as a treatment not only in breast cancer but also in tamoxifen-resistant breast cancer.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Recommended Citation
Dockham, Marcelline, "Effect of Selective TRβ Agonist (GC-1) on ER+ and Tamoxifen Resistant Breast Cancer Cells" (2024). UVM Patrick Leahy Honors College Senior Theses. 628.
https://scholarworks.uvm.edu/hcoltheses/628