Therapeutic Targets and Drugs IV: Telomerase-Specific Gene and Vector-Based Therapies for Human Cancer

Abstract

Recent advances in genetic engineering technology have opened a new avenue of gene-and vector-based therapies for human cancer. For targeting cancer cells, there is a need for tissue- or cell-specific promoters that can express in diverse tumor types but are silent in normal cells. Genetic approaches fostered remarkable insights into the molecular basis of neoplasm, and a number of oncotropic vectors have been thus generated with exceptional properties regarding tumor-restricted specificity. Human telomerase is highly active in more than 85% of primary cancers, regardless of their tissue origins, 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 therapeutic genes in tumor cells. Moreover, oncolytic viruses that combine the specificity of hTERT promoter-based expression systems with the lytic efficacy of replicative viruses are being developed as novel anticancer therapeutics and are currently undergoing the clinical trial. Although these strategies need further refinement to succeed clinically, the hTERT promoter confers competence for selective replication of virus in human cancer, 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.