An Update on the Other Telomerase Inhibitors: Non-G-Quadruplex Interactive Agent, Non-Antisense, Non-Reverse Transcriptase Telomerase Inhibitors

Human telomeres are several kilobases of repeated (TTAGGG)n sequences at the ends of chromosomes, a short fragment of which is lost with each cell division. This shortening serves as a "mitotic clock", limiting the number of divisions which normal somatic cells can undergo. Cells undergoing continuous division need some method of bypassing this clock. One such method is the expression of telomerase, a ribonucleoprotein that rebuilds the lost portion of telomeres. Between 80-95% of tumors are telomerase-positive, including ovarian and hepatocellular carcinoma, neuroblastoma, leukemia/lymphoma, and cancers of the breast, prostate, lung, kidneys and bladder, and many immortalized cell lines. While absent in most normal tissues, it's expressed at higher levels in germline tissues, bone marrow, and lymphocytes. Due to telomerase expression in most tumor cells and its absence in most normal tissues, telomerase inhibitors are being investigated as anticancer agents. This review focuses on non-reverse transcriptase inhibitor, nonoligonucleotide, non-G-quartet interactive agent telomerase inhibitors. These agents include: differentiating agents, kinases and phosphatases, cell cycle and apoptosis regulating agents, immunotherapeutic agents, antibiotics, steroids, bisindole derivatives, and a variety of other compounds, including herbal medical compounds and cyclooxygenase inhibitors. These agents hold great promise for the future treatment of malignancies.