WIN 2011, 6-8 July, 2011, Paris
Development of personalised medicine from animal testing
Professor Soo Khee Chee – National Cancer Centre, Singapore
One of the things that we are doing in our lab is creating animal models of human cancers and the way that we do it is that, as clinicians, when we have explanted tumours from the patients they’re given immediately to the researchers after the pathologists have got what they require for their pathological analysis. This particular researcher of ours is particularly able to engraft human tumours into animals. It has the potential of being a personalised medicine in four different ways, which is very interesting. The first is, though somewhat in the future, because we are able to, in a large majority of cases, implant human tumours into animals, then in many ways the animals are the human models for cancer research and in particular for testing of drugs so that, if the patients do live long enough, by the time the tumours are successfully implanted they can be tested and drug combinations can be used. In a shortened time frame it can then be used to treat the human cancer patients themselves from the tumours that they have given to the animals.
The second way is for different pharma companies, and this is exactly what he is doing, or what we are doing, to have drug combinations given to us for testing on these animal models of human cancers. We talked today about high hurdle of testing of drugs, meaning that if it doesn’t work in animals it’s unlikely to work in humans and this is exactly what we are doing in the lab, that is to have a new pipeline of drugs that are coming from pharmas and having them tested in our human models of cancers. And we are able to successfully tell pharmas which are the drugs that are particularly useful, which are the ones that are not. What is interesting, and this is something which is highlighted in this particular conference, was that in the large majority of cases single drugs don’t work. A combination of drugs are especially useful in the animal models and this is very important feedback for the pharmas because then they can either kill the drug because it doesn’t work in animals or if they work particularly well in animal models that we have of cancers which are common to our countries – liver cancers, stomach cancers, ovarian cancers, then it can lead to further drug development.
The third thing that is very interesting in our lab is that when we are using drug combinations we have an opportunity to study the biology of the cancer because when we use different drugs we find that certain pathways are up-regulated, others are down-regulated and the drugs which are well known to target certain pathways will give insights as to how cancer escapes the treatment and how they become resistant. So that’s great insights that we develop from having this particular lab.
Fourthly, and in an interesting manner, because our lab has drugs coming from many different companies, what actually is happening is that the hype really resides in the fact that we have various drug combinations from different drug companies and we will be able to tell which are the ideal combinations between companies, though they may not know it. The interesting thing is that if we have identical labs all over the world doing that, you might be acting in an interesting manner as the matchmaker for pharma companies because we are the repository of information because we have the new drug pipelines in the lab itself. So in many ways, in an interesting manner, not directly looking at the tumours but looking at the animal models of the tumours, we are able to advance the cause of personalised medicine.
Are there advantages to working directly with animal cases over observing cases in humans?
The human cancer system is better but it doesn’t lend itself to the experimentation that you can do on the mouse models. We have also tested the genomic aberrations in these tumours after several passages and clearly the longer down the passages you go, it will mutate. But the first few passages, then they are near identical to the original human tumour.
We have had interesting results, as I have alluded to, of using, for example, an mTOR inhibitor with a VEGF inhibitor of different companies and we have, in many ways, taken it from the bench to the bedside because from the results that we obtained, we did a phase I trial, we have done a phase II trial and seen some complete responses from the phase II trial and now are waiting to do the phase III trials.
What is the current state of clinical trials within personalised medicine?
What I found interesting is that it may be near impossible for investigator initiator trials to really take place because of the high expenses involved in conducting such trials - the high regulatory requirements that are required, the standardisation, the audit that needs to take place, and then then the need for new drugs in the pipeline to be given to investigators. So clearly, and almost inevitably I suggest, investigators will have to work with big pharmas to push the agenda for this personalised medicine.