Landmark study raises hopes for new cancer drugs
FRIDAY 5 SEPTEMBER 2008
US scientists have deciphered part of the structure of telomerase, an enzyme which keeps cells in an 'immortal' state and is active in more than eight out of ten human cancers.
The active region of telomerase adds multiple copies of a short DNA sequence to the ends of chromosomes, thus helping to prevent damage and the loss of genetic information during cell division.
While the enzyme is active in cells that multiply frequently, such as embryonic stem cells, it is switched off in most adult cells to prevent unwanted cell growth.
Fundamental research like this may help scientists to design drugs that block telomerase and could potentially be used to treat a wide range of cancers.
- Liz Baker, senior science information officer, Cancer Research UK
However, many cancer cells regain the ability to activate telomerase, allowing them to replicate uncontrollably.
A team at the Wistar Institute in Philadelphia has now worked out the structure of the active region, paving the way for the creation of new cancer drugs that shut down the enzyme and stop unwanted cell division.
Lead researcher Dr Emmanuel Skordalakes, assistant professor in Wistar's Gene Expression and Regulation Programme, commented: "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."
The team used a gene from the red flour beetle which produces stable telomerase in copious amounts, providing sufficient quantities for their study.
They then used a technique called X-ray crystallography to determine the three-dimensional structure of the enzyme's active region.
Dr Skordalakes said that the results are "extremely exciting. For the first time, we can see how telomerase assembles at the end of chromosomes to initiate telomere replication".
They now plan to search for drugs that deactivate the enzyme and that could represent new anti-cancer therapies.
Liz Baker, senior science information officer at Cancer Research UK, said: "This is a crucial part of the puzzle in understanding how telomerase works. Fundamental research like this may help scientists to design drugs that block telomerase and could potentially be used to treat a wide range of cancers."
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