Telomerase Inhibition as a Selective Anticancer Therapy

The long-term objective is to discover and develop an entirely new class of anticancer drugs that1) has a novel mechanism of action, 2) is more specific and less toxic than traditional drugs, and 3) hasthe potential to treat a wide variety of cancers. We will assess the validity and feasibility of using theenzyme telomerase as an innovative target to develop a mechanism-of-action-based drug discoveryeffort. The concept that telomerase is unique and essential for immortality in tumor cells was pioneeredby heron's scientists and advisors. In normal somatic cells, telomerase is absent and telomeres, theends of chromosomes, gradually shorten, ultimately causing permanent cell-cycle arrest. Most malignantcells, however, maintain short, stable telomeres through the activation of telomerase, the enzyme whichsynthesizes telomeric DNA. Thus, we will survey a wide variety of normal and malignant tissues andcell lines for telomere length and expression of telomerase. We will then develop an automatedhigh-throughput screen to identify inhibitors of telomerase from a number of large and structurallydiverse compound libraries. Active compounds will be selected for further analysis and ultimately clinicaldevelopment.