In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. LB-101-LB-101
Abstract:
Background: Triple negative breast cancer is characterized by a lack of expression of both estrogen and progesterone receptor as well as lack of amplification of HER2. Patients with triple negative breast cancer carry an unfavorable prognosis compared to other breast cancer subtypes given that endocrine or HER-2 targeted therapies are not effective, rendering chemotherapy the sole effective treatment option to date. In a previous work by Liedtke et al. ((Liedtke et al., Cancer Res 2009) we generated a list of genes, which showed higher expression in triple negative breast cancer and, in addition, are known to encode targets for known non-oncologic drugs. These gene products might represent targets for future therapies of triple negative breast cancer. Results: We could identify SRD5A1, which encodes the type-1 isoform of the steroid-5-alpha-reductase, showing a higher expression in triple negative breast cancer both in vivo and in vitro. Dutasteride is a dual blocker of both the type-1 and type-2 isoform of SRD5A1 and is indicated in the treatment of benign prostate hyperplasia. Treatment of triple negative breast cancer cell lines with dutasteride was associated with a dose-dependent decrease in cell viability, altered protein expression of VEGF and HIF-1α and increased chemosensitivity. Conclusion: Our results demonstrate that firstly, using differential gene expression analysis in clinically relevant breast cancer subtypes, potential new drug targets can be generated. Secondly, we identified the SRD5A1-corresponding anti androgenic drug dutasteride as a combinatorial therapeutic option besides standard chemotherapy in highly aggressive triple negative breast cancer. Citation Format: Marie-Kristin von Wahlde, Carolin Huelsewig, Christian Ruckert, Martin Götte, Ludwig Kiesel, Cornelia Liedtke, Christof Bernemann. The antiandrogen drug dutasteride sensitizes triple negative breast cancer cells to chemotherapy via HIF-1α / VEGF-signaling. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-101. doi:10.1158/1538-7445.AM2014-LB-101
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2014-LB-101
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2014
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
