Lung cancer is a leading cause of cancer death due to the
high incidence of metastasis; therefore, novel and effective
treatments are urgently needed. A current strategy is
cancer-specific targeted gene therapy. Although many
identified that cancer-specific promoters are highly
specific, they tend to have low activity compared with
the ubiquitous cytomegalovirus (CMV) promoter, limiting
their application. We developed a targeted gene therapy
expression system for lung cancer that is highly specific
with strong activity. Our expression vector uses the
survivin promoter, highly expressed in many cancers but
not normal adult tissues. We enhanced the survivin
promoter activity comparable to the CMV promoter in
lung cancer cell lines using an established platform
technology, whereas the survivin promoter remained weak
in normal cells. In mouse models, the transgene was
specifically expressed in the lung tumor tissue, compared
with the CMV promoter that was expressed in both
normal and tumor tissues. In addition, the therapeutic
gene BikDD, a mutant form of pro-apoptotic Bcl2
interacting killer, induced cell killing in vitro, and
inhibited cell growth and prolonged mouse survival
in vivo. Importantly, there was virtually no toxicity when
BikDD was expressed with our expression system. Thus,
the current report provides a therapeutic efficacy and safe
strategy worthy of development in clinical trials treating
lung cancer
