HDAC Inhibitors Induce LIFR Expression and Promote a Dormancy Phenotype in Breast Cancer

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2021 Jul 11

PMID 34247191

Citations 15

Authors

Miranda E Clements

Lauren Holtslander

Courtney Edwards

Vera Todd

Samuel D R Dooyema

Kennady Bullock

Kensey Bergdorf

Cynthia A Zahnow

Roisin M Connolly

Rachelle W Johnson

Affiliations

Soon will be listed here.

Abstract

Despite advances in breast cancer treatment, residual disease driven by dormant tumor cells continues to be a significant clinical problem. Leukemia inhibitory factor receptor (LIFR) promotes a dormancy phenotype in breast cancer cells and LIFR loss is correlated with poor patient survival. Herein, we demonstrate that histone deacetylase inhibitors (HDACi), which are in phase III clinical trials for breast cancer, epigenetically induced LIFR and activated a pro-dormancy program in breast cancer cells. HDACi slowed breast cancer cell proliferation and reduced primary tumor growth. Primary breast tumors from HDACi-treated patients had increased LIFR levels and reduced proliferation rates compared to pre-treatment levels. Recent Phase II clinical trial data studying entinostat and azacitidine in metastatic breast cancer revealed that induction of several pro-dormancy genes post-treatment was associated with prolonged patient survival. Together, these findings suggest HDACi as a potential therapeutic avenue to promote dormancy, prevent recurrence, and improve patient outcomes in breast cancer.

Citing Articles

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