Geburtshilfe Frauenheilkd 2018; 78(10): 182
DOI: 10.1055/s-0038-1671301
Poster
Freitag, 02.11.2018
Gynäkologische Onkologie II
Georg Thieme Verlag KG Stuttgart · New York

KDM 4 Inhibition targets breast cancer stem-like cells

S Stepputtis
1  Uniklinik Freiburg, Department of Urology, Freiburg, Deutschland
,
E Metzger
1  Uniklinik Freiburg, Department of Urology, Freiburg, Deutschland
,
E Stickeler
2  Uniklinikum Aachen (RWTH), Gynäkologie, Aachen, Deutschland
,
R Schüle
1  Uniklinik Freiburg, Department of Urology, Freiburg, Deutschland
,
J Maurer
2  Uniklinikum Aachen (RWTH), Gynäkologie, Aachen, Deutschland
› Author Affiliations
Further Information

Publication History

Publication Date:
20 September 2018 (online)

 

Traditional treatments for breast cancer fail to address therapy-resistant cancer stem-like cells that have been characterized by changes in epigenetic regulators such as the lysine demethylase KDM 4. Here we describe an orally available, selective and potent KDM 4 inhibitor (QC6352) with unique preclinical characteristics. To assess the anti-tumor properties of QC6352, we established a method to isolate and propagate breast cancer stem-like cells (BCSC) from individual triple-negative tumors resected from patients after neoadjuvant chemotherapy. Limiting-dilution orthotopic xenografts of these BCSC regenerated original patient tumor histology and gene expression. QC6352 blocked BCSC proliferation, sphere formation and xenograft tumor formation. QC6352 also abrogated expression of EGFR which drives the growth of therapy-resistant triple-negative breast cancer cells. Our findings validate a unique BCSC culture system for drug screening and offer preclinical proof of concept for KDM 4 inhibition as a new strategy to treat triple-negative breast cancer.