Research Project
6103091
Tumor cells possess the capacity for unlimited replication. This immortal phenotype is, ultimately, the reason why they produce death in cancer patients. Clinically used and-cancer regimens, as well as those under experimental evaluation, generally attempt to contain this growth potential either through reducing the tumor burden (e.g., with surgery, cytotoxic/cytostatic agents, or radiation), manipulating the environment of the tumor, or attempting to reinstate cell cycle controls. Telomerase inhibition is the only therapeutic target that aims at reversing the immortal phenotype of tumor cells. Because of the novelty of this approach, no telomerase inhibitors have yet been developed for human therapeutic use. Furthermore the complete human enzyme has not yet been purified or cloned. Thus, it is not possible at this point to design telomerase inhibitors rationally. An empirical approach using high-throughput screening will, therefore, be used to discover telomerase inhibitors. Active compounds will also be profiled in secondary assays to establish their specificity. Successive rounds of chemical modification followed by testing in the screen and secondary assays will be used to improve the potency and specificity of the most promising compound(s). When sufficient potency and specificity are achieved, the compound will be tested in ex vivo, and, finally, in vivo tumor models.
