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Cancer Cell. 2011 Sep 13;20(3):341-56. doi: 10.1016/j.ccr.2011.07.017.

BikDD eliminates breast cancer initiating cells and synergizes with lapatinib for breast cancer treatment.

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  • 1Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, USA.

Abstract

Breast cancer initiating cells (BCICs), which can fully recapitulate the tumor origin and are often resistant to chemo- and radiotherapy, are currently considered as a major obstacle for breast cancer treatment. Here, we show that BIKDD, a constitutively active mutant form of proapoptotic gene, BIK, effectively induces apoptosis of breast cancer cells and synergizes with lapatinib. Most importantly, BikDD significantly reduces BCICs through co-antagonism of its binding partners Bcl-2, Bcl-xL, and Mcl-1, suggesting a potential therapeutic strategy targeting BCICs. Furthermore, we developed a cancer-specific targeting approach for breast cancer that selectively expresses BikDD in breast cancer cells including BCICs, and demonstrated its potent antitumor activity and synergism with lapatinib in vitro and in vivo.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:
21907925
[PubMed - indexed for MEDLINE]
PMCID:
PMC3172580
Free PMC Article

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