Cancer enzyme structure uncovered

Monday September 1 2008

“New hope of cure for all cancers” is the headline in the Daily Express . Scientists have “unravelled the enzyme that helps to spread cancer cells” and that this may pave the way to “one size fits all” drugs. The newspaper goes on to say that for more than a decade researchers have been investigating an enzyme called telomerase, which is important for normal cell growth but also plays a part in proliferation of cancer cells. Researchers have now “worked out the most important part of its structure”, the newspaper adds.

The study behind this story has looked at the structure of the subunits that make up telomerase. Understanding the structure of this enzyme – which is involved in ageing and in cancer – may one day lead to the development of cancer drugs that rely on blocking its negative activity. It will be some time before we see these drugs, given the large amount of development and testing that must now begin, but the results are a key step in furthering research into treatments for cancer based on the action of this enzyme.

Where did the story come from?

The research was led by Emmanuel Skordalakes and colleagues from the Wistar Institute in Philadelphia, US carried out this study. The study was funded by the Pennsylvania Department of Health and the Ellison Medical Foundation. It was published in the peer-reviewed medical journal: Nature .

What kind of scientific study was this?

This was a laboratory study where researchers were investigating the molecular structure of one part of telomerase. Telomerase is an enzyme that plays a crucial role in ensuring genetic stability in cells that are actively dividing and growing. Over time, telomerase becomes less active and this leads to ageing. However, in cancer cells, telomerase is over expressed (over active) and this helps to give these cells immortality. Because of these properties, telomerase has been the focus of a lot of research into ageing and into cancer.

The researchers used the genes that code for the manufacture of telomerase from flour beetles (Tribolium castaneum ), which they inserted into bacteria (E. coli ) to manufacture it in large quantities. They extracted a subunit of telomerase called TERT from the bacteria and purified it using complex methods. Further laboratory investigation (including co-crystallisation) was used to investigate the structure. This publication reports the findings about the structure of the protein subunit of telomerase.

What were the results of the study?

The researchers found that TERT is organised into a ring configuration. This structure is similar to that of other enzymes, including reverse transcriptase, suggesting there may be an evolutionary link. The researchers present detailed descriptions and illustrations of TERT, including models of how TERT binds with RNA and DNA.

What interpretations did the researchers draw from these results?

The researchers conclude that “because telomerase has a critical role in both cancer and ageing, these findings could potentially assist our efforts to identify and develop inhibitors and/or activators of this enzyme for the treatment of cancer and ageing, respectively”.

What does the NHS Knowledge Service make of this study?

This laboratory study has solved a crucial part of the puzzle surrounding the role of telomerase in ageing and in cancer. By uncovering the structure of key parts of this enzyme, the researchers have potentially opened up a new avenue of research for medications to treat cancer. However, such treatments will be some way off. Karol Sikora, a leading cancer expert, is quoted in the Daily Express as saying that the discovery is probably five years away from reaching clinical trials (i.e. human studies).

Sir Muir Gray adds...

Important study but there’s five or 10 years to go.

Analysis by Bazian
Edited by NHS Choices