Study opens door to new cancer, ageing treatments

September 1st, 2008 - 3:27 pm ICT by IANS  

Washington, Sep 1 (IANS) Researchers have deciphered the structure of telomerase, an enzyme that plays a key role in the development of nearly all human cancers. The landmark achievement opens the door to the creation of new, broadly effective cancer drugs, as well as anti-aging therapies.

Researchers have attempted for more than a decade to find drugs that shut down telomerase-widely considered the primary target for the development of new cancer treatments-but have been hampered in large part by a lack of knowledge of the enzyme’s structure.

The findings should help efforts to design effective telomerase inhibitors, said Emmanuel Skordalakes, assistant professor in Wistar Institute’s Gene Expression and Regulation Program, who led the study.

“Telomerase is an ideal target for chemotherapy because it is active in almost all human tumours, but inactive in most normal cells,” Skordalakes said. “That means a drug that deactivates telomerase would likely work against all cancers, with few side effects.”

The study elucidates the active region of telomerase and provides the first full-length view of the telomerase molecule’s critical protein component. It reveals surprising details, at the atomic level, of the enzyme’s configuration and how it works to replicate the ends of chromosomes - a process critical to both tumour development and the aging process.

In humans, telomerase adds multiple repeats of a short DNA sequence to the ends of chromosomes, known as telomeres, thus preventing damage and the loss of genetic information during cell division.

When telomerase is dormant, telomeres shorten each time a cell divides, leading eventually to genetic instability and cell death. By preserving chromosomes’ integrity, telomerase allows cells to continue living and dividing.

The enzyme is active in cells that multiply frequently, such as embryonic stem cells, but is switched off almost entirely in normal adult cells to prevent the dangers of runaway cell proliferation.

Cancer cells, however, often regain the ability to activate telomerase, which has been implicated in 90 percent of human tumors. The enzyme permits cells to replicate indefinitely and achieve the cellular “immortality” that is the hallmark of cancer. Deactivating telomerase would stop tumor growth.

In addition to its role in cancer, telomerase holds significant implications for the development of therapies to combat aging and other age-related diseases.

Finding ways to activate telomerase under controlled conditions and allow some cells to begin dividing again could result in healthier, younger-looking tissue that lives longer.

“That was really the breakthrough,” Skordalakes says. “Once we found that the gene from this organism expressed the protein in the quantities we needed, we were able to move quickly.”

The study was published online in the Sunday edition of Nature.

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