Telomerase inhibitors and vaccines for the treatment of cancer

Telomeres are nucleotide sequences with a repeating string of TTAGGG, which are between 3 and 20 kilobases in length and located at the terminal region of chromosomes in most eukaryotic organisms. The telomere acts to protect chromosomal and genetic integrity during the process of cellular replication. However, the structure of the telomere becomes shortened during each cell replication. As mammalian telo meres shorten, eventually cells reach their replication limit and progress into cellular aging. This process eventually results in the halting of cell proliferation and leads to cellular senescence and cell death. Telomerase is a reverse transcriptase enzyme which functions to produce telomere lengthening, and thus to preserve the integrity of chromosomes and chromosomal replication ability. Cancer cells bypass the senescence observed in normal cells and become immortalized because of telomere extension, which is thought to be due in large part to the activation of telomerase. Many types of cancer cells have been reported to contain elevation of telomerase enzyme activity. Therefore, inhibition of telomerase activity or activation of the immune system to recognize and destroy telomerase-activated cancer cells may be effective therapeutic approaches to prevent the development of existing tumors. In addition, telomerase inhibition may effectively prevent the initiation and progression of many cancers. Furthermore, the monitoring of relative tissue telomerase activity may provide an important diagnostic tool to predict the development and/or progression of malignant or premalignant tissue. This review examines telomerase as a potential therapeutic target for cancer and therapeutic approaches to inhibit telomerase activity. Many of these therapeutic and diagnostic tools are being considered, and several are currently undergoing clinical testing for the treatment of cancer.