"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."
