Telomerase is an enzyme that catalyzes the replacement of short telomeric repeats (TTAGGG)n at the ends of chromosomes and thus maintains the length of telomeres. Loss of telomeric DNA results in senescence whereas strong telomerase activity results in cell immortality. Telomerase Is now established as a sensitive and specific marker for cancer. In various neoplasms1 it has also been shown that telomerase activity may be used as a marker for detecting pre-cancerous tissue or early stage of malignancy and may also be used for predicting patient survival. with the cloning of the telomerase gene/s (TRT/EST2 and TPI) it is now possible to develop simple and rapid antibody based methods for cancer diagnosis for use in clinical laboratories. Recently, other key factors including TRF1, TRF2 and Tankyrase that regulate telomere length through distinct mechanisms have been cloned. In this feasibility study, we propose to develop highly specific monoclonal antibodies to TRT, TP1, TRF1, TRF2 and Tankyrase. Through the use of cell line/tissue models we will evaluate their utility for diagnosis of cancers. In our Phase II proposal, the selected panel of reagents will be tested extensively against a large number of patient tumors to test whether patterns of expression of these factors may be related with early stages of malignancy.
Presently, there are no monoclonal antibodies to telomerase and telomer associated factors. As this area is presently the subject of intensive study, antibodies to telomerase and other telomere--associated factors will have utility not only in research, but also in diagnosing cancers and pre- cancerous states and monitoring therapy.
