Telomerase as an anti-cancer target: current status and future prospects.

Abstract

As is common with a newly discovered cancer-associated gene/protein, there is a lag between the elucidation of its cellular and molecular biology and appropriate therapeutic intervention. Telomerase represents an interesting and promising anticancer drug target but poses a particular drug discovery challenge. It is unclear at present what is the optimum means of targeting this complex ribonucleoprotein and associated telomeric DNA and binding proteins: various strategies are actively being explored. Some recent data (e.g. 2-5A antisense against telomeric RNA, targeting TRF2, introduction of dominant-negative hTERT into cells) has raised doubts over the previously presumption of a requirement for prolonged enzyme inhibition with gradual telomere erosion, especially in tumour cells with relatively short telomeres. Highly potent and selective in vivo inhibitors are required to validate the target and address these critical issues.