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New drug to stop cancer spread?

The Daily Express has reported of a “drug hope in the battle to stop cancer spreading”.  It said that scientists have found a new group of molecules that could stop the spread of cancer and “lead to new drugs”.

The news report is based on complex early-stage laboratory research aimed at inhibiting a type of enzyme that is fundamental to certain biological processes in cells. By doing this, it is theoretically possible that certain disease processes, including the spread of cancer, can be prevented. The researchers reported some success in inhibiting this process, and this research will be of great interest to other scientists in the same field.

Importantly, the researchers state that this is a “very early step in the drug development process”. This is a key point, and if these early findings do form the basis for new drug development, it will be many years in development and testing.

Where did the story come from?

The study was carried out by Thomas Pesnot and colleagues from the University of East Anglia and Carlsberg Laboratory, Copenhagen, Denmark. The research was funded by the UK Engineering and Physical Sciences Research Council, UK Medical Research Council, Leverhulme Trust and Danish Agency for Science, Technology and Innovation. The paper was published in the peer-reviewed scientific journal Nature Chemical Biology.

In the main, the Express reported this laboratory research well. However, the eye-catching headline of “drug hope” and the report that millions of lives could be saved are premature at this very early stage in the research.

What kind of research was this?

This laboratory research examined glycosyltransferases (GTs). These enzymes play a key role in many important biological processes at the cellular level. The researchers were interested in these enzymes because, in theory, inhibiting the right GTs could potentially affect a number of health and disease processes in humans, including cancer spread.

GTs are carbohydrate enzymes that facilitate the transfer of simple sugars from a “glycosyl donor” (such as a nucleotide [a base unit of DNA] that is linked to a sugar molecule) to an acceptor molecule (for example a glycan, peptide or lipid).

The researchers say that, until now, there has been a lack of structural information about GTs, preventing the design of a GT inhibitor. In this research, they have reportedly succeeded in synthesising a GT donor molecule that inhibits five different GTs.

What did the research involve?

This research involved a type of GT called Leloir-type galactosyltransferases (GalTs) and their usual donor molecule, UDP-galactose. The researchers developed an alternative synthetic donor molecule, UDP-Gal, which acts as an inhibitor towards five different GalTs. The effect of UDP-Gal on GalTs was examined using type A and B human blood in complex laboratory trials.

What were the basic results?

The researchers found that the new donor molecule, UDP-Gal, effectively “locked” the target GalTs and prevented these particular enzymes from participating in important cellular processes, in particular aiding sugar transfer between DNA and other recipient molecules.

How did the researchers interpret the results?

The researchers concluded that their results have demonstrated inhibition of one particular GalT enzyme. However, as many GTs have similar mechanisms of action, they suspect that their method would be applicable to other enzymes in this class.

Conclusion

This complex early-stage laboratory research investigated the possibility of inhibiting a type of GT enzyme, called Leloir-type galactosyltransferase (GalT). The researchers created a synthetic molecule (UDP-Gal) which, they demonstrated, GalT would target instead of its natural target. This synthetic molecule effectively “locked” the GalT, thereby preventing its usual activity. GTs underlie many biological processes. The researchers believe that the development of this inhibitor means that others could be developed to target other GTs, as these enzymes all have fairly similar mechanisms of action.

This research paper itself does not mention any possible therapeutic implications of this discovery, and makes no mention of cancer. However, one of the researchers said in the Express: ‘In cancer cells you find the natural molecule UDP-Galactose. We have made a synthetic modification of this molecule and this works as a blocker. The expectation is, in the next step of research, that this could be a blocker of this cellular spreading of cancer cells as well.”

This is very early research. While other scientists may observe it with great interest, it will be many years before a practical application, such as a new cancer drug, will be possible.

Links to the headlines

Cancer: drug hope in the battle to stop disease spreadingDaily Express, April 6 2010

Links to the science

Pesnot T, Jørgensen R, Palcic MM and Wagner GK. Structural and mechanistic basis for a new mode of glycosyltransferase inhibition. Nature Chemistry Biology, April 4 2010

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