What work are you doing with endothelial cells?
We are working on the mechanisms that modify the vasculature in the tumour. In other words the vessels in the tumour are very different from the rest of the organism: they are enlarged, there is no hierarchical organisation and they are very leaky. So this is an important difference because since the vessels are leaky the tumoural cells can enter into the circulation in a very easy way. On the other side, these vessels tend to regress very readily so many areas of the tumour are not correctly perfused and therefore chemotherapy does not reach all the tumour and there are areas of necrosis, of hypoxia, where cancer stem cells can reside and still maintain vitality and then proliferate.
Are they resistant to radiotherapy because of the hypoxia?
Little by little from the first idea that was simply let’s reduce tumour vascularisation with antiangiogenic drugs, now the concept is strongly evolving. So the idea is that there are steps of progression of the tumour where it is much better to normalise the vasculature, so to make it even more resistant and to make the vessel able to perfuse all the tumour. Then possibly when the tumour is reduced then in this condition you might induce regression of the vasculature and, possibly together with the chemotherapy or irradiation, induce a further improvement in the growth of the tumour and also, of course, reduce the metastatic dissemination.
Are you involved in stem cell work around the vasculature?
We are doing some work about that because we are convinced that besides the endothelial cell progenitor that can be released from the bone marrow there are also progenitors present already in the vasculature. These cells can proliferate under specific growth factors and strongly promote further proliferation of the vasculature in the tumour. So it would be very important to identify these progenitors and even if they are certainly present in low numbers to be able to target them and to see their specific activity in this environment.
Are you looking to move into the clinic?
Absolutely, yes. Indeed, there are already a series of treatments that are directed to normalisation of the vasculature and they are under study because all the preclinical studies have been completed now and they are under study to go to the human clinical studies.
What is your view on the satellite institutes?
Science is moving very quickly to the east of the world and certainly Japan and India and China, all these countries, are certainly stronger and stronger in science. So what is very nice is this sort of cross-fertilisation. So it is true that there is some investment of energy or money in this sort of collaboration but still there is a tremendous amount of information and different attitudes. For instance, if I take as an example Bangalore, we realised that their philosophy is different from ours in the sense that they’re studying small animals, insects, fish, but also human diseases at the same time and they get a lot of inspiration out of new technology and new models that really revitalise all our science that was before very much linked to North America and to a certain point of view and news that we receive from the different meetings. So in this case it’s really very, very inspiring, this type of collaboration. For instance, I was talking yesterday to ... and he was telling me about a new type of tomato where the evolution is induced by a virus which changed the DNA of this tomato and then the virus disappeared. But this introduced a new technology that is able now to change the genes in a very quick way. So starting from an observation coming from a tomato and a virus then you get a very nice application to our needs.
