Effect of Selective TRβ Agonist (GC-1) on ER+ and Tamoxifen Resistant Breast Cancer Cells
Dockham, Marcy
Dockham, Marcy
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Abstract
In 2020, the most frequently diagnosed cancer was female breast cancer, with 2.3 million new diagnoses. The estrogen receptor-positive/HER2 negative (ER+/HER2-) breast cancer subtype is the most common, reflecting 50-60% of all breast cancer and having a lower relapse rate than other subtypes. In ER+ breast cancer, five years of tamoxifen reduced the recurrence rate of breast cancer over ten years. However, ER+ tumor cells can be resistant to tamoxifen or develop resistance during treatment. Therefore, there is an urgent need for novel therapeutic interventions. The presence of thyroid hormone receptor beta (TRβ) has been shown in tumor types and demonstrates tumor-suppressive features. The alternate thyroid hormone receptor isoform, TRα, has cardiovascular impacts and predicts a negative prognosis in breast cancer. Selective activation of TRβ using Sobetirome (GC-1), a synthetic thyroid hormone selective for TRβ, exhibits reduced ER+ cell growth and cancer stem cell formation, and increases the efficacy of tamoxifen [Carr lab]. This project aims to first determine the impact of GC-1 on the growth of ER+ cells in the presence of estrogen and presence or absence of tamoxifen, and then identify the effect on tamoxifen-resistant cells (MCF7-TAM-R) in the presence of GC-1.
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Date
2023-01-01