Tuesday 19 February 2013

Of Mice and Men

I’ve written about the state of cancer research on a number of occasions in the past, in particular focusing on the use of different models of cancer – for example here: http://www.anticancer.org.uk/2012/05/wrong-models-of-cancer-part-2.html and here: http://www.anticancer.org.uk/2012/04/standards-in-cancer-research.html and here: http://www.anticancer.org.uk/2011/11/test-tube-cancer-cells-and-people.html. So I hope it’s not getting repetitive to raise the subject again in the light of an important new paper in the Proceedings of the National Academy of Sciences (PNAS). The paper, Genomic responses in mouse models poorly mimic human inflammatory diseases is not about cancer as such, but it’s as important and relevant as any paper on cancer.

The opening line of the paper makes plain why these results are important:
A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials.

And it’s true enough in most areas of medicine, but none more so than in cancer research, where the mouse model is king. But the only problem is that mouse models don’t always match human disease profiles at all well. In the specific case that this paper outlines, it turns out that mouse models of massive inflammatory responses in critically ill patients are miles apart. To quote from the paper again:
The success rate is even worse for those trials in the field of inflammation, a condition present in many human diseases. To date, there have been nearly 150 clinical trials testing candidate agents intended to block the inflammatory response in critically ill patients, and every one of these trials failed.

The reason for this divergence turns out to be because the relationship between genes changed in human patients bears little relationship to the genes expressed in the mouse models of the diseases – the relationship is pretty much random. However, for years scientists who have been studying these diseases have focused on drugs that work for mice and then these drugs have subsequently failed in humans. Not only has this cost millions, it also means that much research effort has been wasted in targeting genes that have nothing to do with human diseases. It also means that potentially useful drugs have been abandoned precisely because they failed to do anything in mice.
And it’s not just inflammatory diseases at stake – the same is true in cancer research. We can only speculate on how much money, effort and intellectual energy has been wasted on research that doesn’t apply to people. The reliance on test tubes and mouse models means that much time and effort has been for nothing.

Something needs to change.

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