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Inhibition of Telomerase:Is it Promising for Cancer Therapy?

© David Olle

In 1994, researchers in cell biology announced a bold discovery that promised to reveal secrets of cancer and aging. Earlier work had shown that the tips of all chromosomes of cells have fragments of DNA called telomeres that protect the integrity of the chromosomes during cell division. With each cell division, however, a bit of the telomere is lost until it becomes too short to protect the chromosome from break-up and entanglement with other chromosomes. At this point, after about 50 cell divisions, the cell stops dividing, enters a stage called senescence, and soon dies. In the late 80's, researchers found an enzyme called telomerase that serves to maintain the length of telomeres by resynthesizing the sections lost. In so doing, the cells can continue to divide. In 1994, it was discovered that cancers have the ability to reactivate the telomerase enzyme, but, circumventing the normal processes, continue to divide with no checks and balances. Although immortality is ancient dream of mankind, it is the last thing we want when it refers to cancer cells.

Before a cell can divide, the DNA of the chromosomes must duplicate itself. DNA is built up of molecular units called nucleotides, which come in four types abbreviated as A, C, G, and T. Although most of the DNA consists of long complex nucleotide sequences that hold the genetic code, the telomere sections have much simpler sequences repeated many times 1. The telomere sections have no known function in the genetic code. Each process of duplication results in the loss of a small section of the DNA. The telomere acts as a sort of sacrificial lamb; by losing part of its length, the essential DNA sequences are retained.

Telomerase is normally active only when it is important for cells to continue multiplying, such as during embryonic development. After birth, telomerase becomes inactive, except for the production of sperm cells in the male. However, telomerase activity has been found in up to 90% of all cancers, and has shown promise as a diagnostic tool. In certain cancers, increased activity levels may identify patients that have either favorable or unfavorable prognostic outcomes; while in other cases can distinguish between benign and malignant tumors.

The medical establishment received the report on the relationship between telomerase and cancer with great enthusiasm. Researchers foresaw the development of telomerase inhibitors as new and unique weapons against cancer. After all, if the telomerase in cancer cells could be disactivated, the cancer cells would stop dividing and die after a period like normal cells. Since then, reality has set in, and some unique problems in the development of telomerase inhibitors as therapeutic agents have become apparent.

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