Inhibition of Telomerase as a Therapeutic Target for the Treatment of Prostate Cancer

摘要

Malignant prostate cells must divide many times to form a tumor, metastasize or recur after therapy. Critical for this type of endless cell division is an enzyme named telomerase. This enzyme is usually dormant in most normal tissues, but is resurrected in prostate cancer cells by yet unknown genetic changes. Since the enzyme is required for survival of cancer cells but is not present in most normal cells, inhibition of telomerase may specifically target prostate cancer cells. We have shown that impeding the function of telomerase by expressing a mutated version of this protein kills prostate cancer cells in an experimental setting. We now wish to translate this finding into a more practical application by searching for smaller molecules capable of inhibiting telomerase activity. The approach we propose to take is one that capitalizes on reagents already in hand. First, we have mapped parts of telomerase that are extremely sensitive to even small disruptions. We now wish to find molecules that bind to these sensitive regions, as such regions represent the most attractive parts of the protein to target for inhibition. We will therefore screen millions upon millions of small molecules, termed peptides, for those few that adhere to these regions of the telomerase enzyme. Such peptides could serve as a blueprint to develop even more clinically relevant inhibitors of telomerase.