Abstract
Conditionally replicating adenoviruses (CRADs) represent a novel approach for treating neoplastic diseases. In this study, we utilized two infectivity enhanced CRADs containing tumor specific promoters for controlling replication of the viruses in the context of cervical cancer. RGDCRADcox-2R has the cyclooxygenase-2 (cox-2) promoter controlling expression of E1A. Cox-2 is the rate-limiting enzyme in prostaglandin synthesis, and it is involved in control of inflammatory reactions. Recently, it has been shown that cox-2 is expressed in many epithelial cancers, and it is related to carcinogenesis and tumor angiogenesis. We also evaluated the efficacy of a CRAD utilizing the vascular endothelial growth factor (VEGF) promoter. VEGF has an important role in the induction of tumor-associated angiogenesis, and it is often highly expressed during tumorigenesis. Expression of cox-2 and VEGF in cervical cancer cell lines and patient tumor specimens has been demonstrated. Further, the regulation and control of cox-2 and VEGF expression may be closely linked.
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