Replication-selective tumor-specific viruses present a novel approach for 
treatment of neoplastic disease. These vectors are designed to induce 
virus-mediated lysis of tumor cells after selective viral propagation within the 
tumor. For targeting cancer cells, there is a need for tissue- or cell-specific 
promoters that can express in diverse tumor types and are silent in normal 
cells. Recent advances in molecular biology have fostered remarkable insights 
into the molecular basis of neoplasm. Telomerase activation is considered to be 
a critical step in carcinogenesis and its activity correlates closely with human 
telomerase reverse transcriptase (hTERT) expression. Since only tumor cells that 
express telomerase activity would activate this promoter, the hTERT proximal 
promoter allows for preferential expression of viral genes in tumor cells, 
leading to selective viral replication. We constructed an attenuated adenovirus 
5 vector (Telomelysin, OBP-301), in which the hTERT promoter element drives 
expression of E1A and E1B genes linked with an internal ribosome entry site 
(IRES). Telomelysin replicated efficiently and induced marked cell killing in a 
panel of human cancer cell lines, whereas replication as well as cytotoxicity 
was highly attenuated in normal human cells lacking telomerase activity. Thus, 
the hTERT promoter confers competence for selective replication of Telomelysin 
in human cancer cells, an outcome that has important implications for the 
treatment of human cancers. This article reviews recent findings in this rapidly 
evolving field: cancer therapeutic and cancer diagnostic approaches using the 
hTERT promoter.