Telomerase - strategies to exploit an important chemotherapeutic target.
Telomeres, unique protein-DNA complexes located at the chromosome ends, have important functions involving both DNA protection and cellular signalling. Telomere structure is very dynamic yet tightly controlled. One important factor is the presence of telomerase, a telomere-specific DNA polymerase activated in a majority of cancer cells. Cancer and normal cell telomeres may have dissimilar structures due to variances in telomere length, telomerase activity and levels of telomere binding proteins. In designing compounds to strictly target cancer cells, these distinctions should be investigated. Much of the recent focus has been on the development of highly effective telomerase inhibitors. Another novel group of small molecules target telomere DNA, thereby disrupting both telomerase activity and telomere structure. This class of compounds should have an immediate impact on cell growth and viability. Since many molecular characteristics of telomeres are unknown, small molecules should also be useful in probing differences in telomere dynamics unique to cancer cells.
Fletcher
Terace M
TM
National Institutes of Health, National Cancer Institute, Division of Basic Sciences, Laboratory of Receptor Biology and Gene Expression, Bethesda, MD 20892-5055, USA. fletchet@exchange.nih.gov