Future Horizons in Lung Cancer
Developing new models in SCLC
Prof Caroline Dive - Cancer Research UK Manchester Institute, Manchester, UK
I gave a talk about developing new mouse models to study small cell lung cancer. These are different from previous models because instead of relying on a biopsy from a patient or an established cell line growing in plastic we take the blood from the small cell lung cancer patient, just 10ml of blood from the arm, we enrich the circulating tumour cells which are very prevalent in this disease, and we take that enriched fraction of the blood and we put it into a mouse with no immune system or poor immune system and those tumours grow on the back of the mice. So that’s really trying to remove as many of the blood cells in the blood stream, because that’s where they live, as we can possibly so they go from a very, very rare subset of cells, which are the circulating tumour cells, in the whole blood to a fraction of that blood sample that has been enriched for those circulating tumour cells so that when that goes into the mouse it still has a lot of blood cells there but we’ve actually enriched for the circulating tumour cells that then grow as the tumour.
What successes have you had so far?
We tried for years to get this to work and finally this happened a couple of years ago. We now have 31 models, the real beauty of the model is that you can take a blood sample before the patient gets any chemotherapy and in about 50% of cases you can grow a mouse model. The patient then responds to that chemotherapy, they then inevitably relapse, sometimes quite quickly, and whilst you would never get another biopsy from that patient with progressive disease, so we don’t know much about progressive disease, they will happily give you another 10ml of their blood. So this is very minimally invasive for the patient and for the first time we get the opportunity to study the biology of this disease at the beginning and then when progressive disease has occurred in the patient after their initial response to chemotherapy. So that gives us a very nice tractable model system to study drug resistance which is the really difficult thing to understand without the biology from those models. So now we can do an experiment that we just couldn’t do before.
How did you arrive at this methodology?
It was really just keep trying until we found a methodology that would work. Once we got it, we’ve now published it, labs all over the world are trying to do what we have done and several of them are beginning to build these models as well which I’m delighted about because I think now we’ve got this new way of looking at small cell lung cancer the faster we can get knowledge about this disease the faster we can make progress with treatment that improves outcomes for patients.
Any final points?
I think the last thing to say about these models is it’s really important that you have a model when you’re testing new therapies that mimics how the patient responds. The only thing we can bench-test, if you like, is chemotherapy because that’s what the patients get. So what’s important about these new models that we call CDX, CTC-derived x-plant models, is that they’re very faithful to the patient. So if we have a patient who responds really well to chemotherapy and then sometime later relapses that’s what we see in the mouse model with the same chemotherapy given to the mouse. If we have a patient who doesn’t respond to chemotherapy the mouse model from that patient also doesn’t respond to chemotherapy. That gives us hope that when we test new agents in these mouse models they are going to actually reflect what might happen in patients who then go into clinical trials.
