Principal Investigator: Chong-xian Pan MD, PhD
Mentor: Chinghai Kao PhD
Scientific Advisor: Lawrence Einhorn MD
Statistician: Beth Juliar MS

Bronchioloalveolar carcinoma (BAC) is highly resistant to chemotherapy and radiation therapy. Currently, the only curative therapeutic approach would be surgical resection of early-stage disease. Most patients succumb to BAC even with the treatment of Gefinitib, an inhibitor to the epidermal growth factor receptor tyrosine kinase. Gene therapy has been clinically ineffective in the treatment of cancer because of failure to deliver sufficient amount of virus to tumor cells secondary to poor specificity of infection and development of neutralizing antibody. BAC is an ideal target for gene therapy because of its inability to invade and easy accessibility of viral delivery. Nevertheless, so far, no virus is available that is specific to BAC. Our laboratory has been working on prostate-restricted replicative adenovirus for several years with very promising results. We have identified that the replication and cell eradication of adenovirus can be restricted to certain cells by controlling the expression of the adenoviral early genes with cell-specific promoters. In this study, we plan to incorporate two promoters into the viral genome to restrict the cell killing into BAC cells only. One of these two promoters is specific to cancer, such as hTERT, and the other one is specific to lung tissue. We anticipate that, by controlling the expression of viral early proteins with these two promoters, the replication and cell lysis of adenovirus will be restricted to BAC cells while sparing the surrounding normal lung tissue. An orthotopic murine BAC model generated with human BAC cells will be studied because it better reflects the pathophysiology of BAC in vivo.