May ultimately replace animal testing and allow metastases analysis
What drugs can be used to treat lung cancer, and how effective are they? Until now, drug companies have had to rely on animal testing to find out. But in the future, a new 3D model lung is set to achieve more precise results and ultimately minimise – or even replace – animal testing.
'Animal models may be the best we have at the moment, but all the same, 75% of the drugs deemed beneficial when tested on animals fail when used to treat humans,' said Professor Dr Heike Walles, Head of the Würzburg-based 'Regenerative Technologies for Oncology' project group at the Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB.
Walles and his team have developed an innovative 3D test system that allows it to simulate what happens in the human body. 'Our plan is for this system to replace animal tests in the future,' he says.
Essentially they have recreated the human lung in miniature – with a volume of half a cubic centimetre, each model is no bigger than a sugar cube. In a parallel effort, scientists at the Department of Bioinformatics at the University of Würzburg are working up computer simulation models for different patient groups. These are necessary because patients may have genetic variations that inhibit therapies from having the desired effect. Comparing the theoretical and biological models allows each research group to optimise their results.
The biological model is based on human lung cancer cells growing on tissue. Thus an artificial lung is created. A bioreactor is used to make it breathe and to pump a nutrient medium through its blood vessels in the same way our bodies supply our lungs with blood. The reactor also makes it possible to regulate factors such as how fast and deeply the model lung breathes.
Essentially they have recreated the human lung in miniature with a volume of half a cubic centimetre
With the scientists having managed to construct the lung tissue, Walles reports that treatments that generate resistance in clinics do the same in this model. Researchers are now planning to explore the extent to which their artificial lung can be used to test new therapeutic agents. Should resistance crop up during testing, doctors can opt to treat the patient with a combination therapy from the outset and thus side-step the problem. Long term, it might be possible to create an individual model lung for each patient. This would make it possible to predict accurately which of the various treatment options will work. The required lung cells are collected as part of the biopsy performed to allow doctors to analyse the patient’s tumour.
As well as using the model lung to test new drugs, it could also help researchers understand the formation of metastases better; it is these that often make a cancer fatal.
'As metastases can’t be examined in animals – or in 2D models where cells grow only on a flat surface – we’ve only ever had a rough understanding of how they form. Now for the first time, our 3D lung tissue makes it possible to perform metastases analysis,' said Walles. 'In the long term, this may enable us to protect patients from metastases altogether.'
In order to travel through the body, tumour cells alter their surface markers – in other words, the molecules that bind them to a particular area of the body. Cancer cells are then free to spread throughout the body through the circulatory system before taking up residence somewhere else by expressing their original surface markers. The scientists plan to use their model lung’s artificial circulatory system to research exactly how this transformation occurs. And in doing so, they may eventually succeed in developing drugs that will stop metastases forming in the first place.