2. Academic Validation
  3. Stratification of Tamoxifen Synergistic Combinations for the Treatment of ER+ Breast Cancer

Stratification of Tamoxifen Synergistic Combinations for the Treatment of ER+ Breast Cancer

  • Cancers (Basel). 2023 Jun 14;15(12):3179. doi: 10.3390/cancers15123179.
Emily K Zboril 1 2,  Jacqueline M Grible 1,  David C Boyd 1 3,  Nicole S Hairr 1,  Tess J Leftwich 1,  Madelyn F Esquivel 1,  Alex K Duong 1,  Scott A Turner 1,  Andrea Ferreira-Gonzalez 1,  Amy L Olex 4,  Carol A Sartorius 5,  Mikhail G Dozmorov 6,  J Chuck Harrell 1 7 8
Affiliations

Affiliations

  • 1 Department of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA.
  • 2 Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA 23298, USA.
  • 3 Integrative Life Sciences Program, Virginia Commonwealth University, Richmond, VA 23298, USA.
  • 4 C. Kenneth and Dianne Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA 23298, USA.
  • 5 Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • 6 Department of Biostatistics, Virginia Commonwealth University, Richmond, VA 23298, USA.
  • 7 Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.
  • 8 Center for Pharmaceutical Engineering, Virginia Commonwealth University, Richmond, VA 23298, USA.
PMID: 37370789 DOI: 10.3390/cancers15123179
Abstract

Breast Cancer alone accounts for the majority of Cancer deaths among women, with the most commonly diagnosed subtype being Estrogen receptor positive (ER+). Survival has greatly improved for patients with ER+ breast Cancer, due in part to the development of antiestrogen compounds, such as tamoxifen. While treatment of the primary disease is often successful, as many as 30% of patients will experience recurrence and metastasis, mainly due to developed endocrine therapy resistance. In this study, we discovered two tamoxifen combination therapies, with simeprevir and VX-680, that reduce the tumor burden in animal models of ER+ breast Cancer more than either compound or tamoxifen alone. Additionally, these tamoxifen combinations reduced the expression of HER2, a hallmark of tamoxifen treatment, which can facilitate acquisition of a treatment-resistant phenotype. These combinations could provide clinical benefit by potentiating tamoxifen treatment in ER+ breast Cancer.

Keywords

ER+ breast cancer; drug synergism; endocrine resistance; estrogen receptor; patient-derived xenograft; tamoxifen.

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