Enzyme discovery may hold key to cancer treatments
Monday 01 September 2008
A major discovery could open the door to "one-fits-all" cancer drugs that can tackle many different forms of the disease.
Researchers have started to unmask an enzyme that plays a major role in the development of nearly all human cancers.
The work may lead to drugs that de-activate the enzyme, and prevent the uncontrolled cell division that leads to cancer.
Experts have been trying for more than a decade to devise anti-cancer therapies that target the enzyme, telomerase. But they have been thwarted by lack of knowledge about the molecule's construction.
Researchers have now deciphered the enzyme's active region and worked out the most important part of its structure.
The new findings, published in the online edition of the journal Nature, reveal atomic-level details of telomerase showing how it works to replicate the ends of chromosomes - a process critical both to tumour development and ageing.
The results are expected to boost development of telomerase inhibitors.
Study leader Dr Emmanuel Skordalakes, from The Wistar Institute in Philadelphia, US, said: "Telomerase is an ideal target for chemotherapy because it is active in almost all human tumours, but inactive in most normal cells. That means a drug that deactivates telomerase would likely work against all cancers, with few side effects."
Telomerase helps prevent the chromosomes - bundles of DNA which contain the genes - suffering damage and the loss of genetic information during cell division.
The enzyme adds protective "caps" known as "telomeres" to the ends of chromosomes which act like the plastic tips on shoe laces that prevent fraying.
When telomerase is dormant, the telomeres shorten each time a cell divides, eventually leading to genetic instability and cell death. This is a key element of the ageing process.
The enzyme is active in cells that multiple frequently, such as immature cells in embryos, but switched off almost completely in normal adult cells.
However cancer cells often regain the ability to activate telomerase, allowing them to replicate indefinitely, and the enzyme has been implicated in 90 per cent of human tumours.
For this reason deactivating telomerase could halt tumour growth.
Unravelling the mysteries of telomerase may also pave the way to therapies that combat ageing and age-related diseases.
Re-activating dormant telomerase in a controlled, safe way, could theoretically produce younger, healthier and longer living tissue.
Understanding telomerase's structure is the first step towards achieving these goals.
But the molecule is complex, made up of multiple protein domains - three dimensional structures that can function independently of each other - as well as a stretch of the genetic "template" RNA.
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