New strategies to inhibit tumor angiogenesis

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Published: 24 Jul 2015
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Dr Elisabetta Dejana, Director of Vascular Biology - IFOM, Milan, Italy

Dr Dejana talks to ecancertv at IFOM EMBL about her work on one of the innovative aspects of anti-cancer therapies, inhibiting tumour growth by blocking blood supply. 

Her study takes a particular focus on brain tumours that currently don't currently have a effective treatment method.

We are particularly interested in understanding how the tumours create their own vascular system and therefore whether we can modify this vasculature, use the vascularisation of the tumour in order to reduce the nutrients and the oxygen from outside but also reduce the capacity of the cancer cells to enter into the systemic circulation and then to metastasise to the different organs.

So during this study we have been more specifically interested in brain tumours that so far do not have an effective therapy.

While we were studying the process through which the tumour was inducing its own vessels we got also interested in the overall organisation of the brain vasculature.

This is a highly specialised type of vasculature that has the difficult task of controlling permeability between blood and the central nervous system.

While we were working on this subject we have been involved in an international network that included North American groups as well as other European groups related to a particular type of cancer, that is endothelial vascular type of tumour.

So we got interested into that and this disease is named cerebral cavernous malformation because it’s a hereditary disease where the patient creates major vascular malformations that look like mulberries, the type of malformation.

They are very fragile and they grow without any control and they keep forming new lesions.

What was also found is that there is the familial type of disease but there is also the sporadic type of disease.

So while the familial disease leads to many malformations during the life of the patient, on the other side the sporadic disease has a very high prevalence and for very high I mean one out of 200 individuals.

In that case this individual only made on malformation but it might have a deleterious effect because these vessels are fragile so there is a continuous leakage of blood which leads to seizures, terrible headaches, eventually paralysis.

At the end they might even develop haemorrhagic stroke with a very high mortality.

So we started to develop in vitro and in vivo experimental models of the disease and we have been able to identify the mechanisms through which these vessels acquire the neoplastic type of differentiation.

Also we have been able to identify one drug that seems to be effective in reducing this malformation.

It is important to underline that so far these patients only have as a therapy the possibility to undergo surgery; that, however, is very dangerous because of the location of this malformation in the brain and in many cases in a very delicate area of the brain.

So the possibility to identify a drug is crucial because this might be a tool through which we hope to reduce the number and size of the malformations.

However, this was also important to establish a link with the Swedish University of Uppsala and in particular Uppsala University offered to me and to my group a very high grant.

So their support is really remarkable, let’s say, and it is spread over ten years of work.

The advantage of having this link, and I also now am a Professor at that University, is to apply a series of facilities that we cannot have so easily here in Milan.

So there is a sort of joint venture between IFOM and Uppsala University on starting with this project but I do hope that will be extended also to other projects in IFOM or in Uppsala with an exchange of students and people.

We have a lab in Uppsala that is starting now.

So what we would like to do is to use their facilities and in particular the robotic huge screening type of facilities that allow us to screen about 100,000 different chemicals and compounds and taking advantage of all the assays that we already developed for screening in a much, much smaller size different drugs.

In this case we hope to be able to identify other chemicals that might be even more effective than the ones we identified so far.

So this is one of the projects but, as I said, in Uppsala there are many more facilities on proteomic, genomic and so on so I think that it would be an important step also in improving the quality not only of my group or the research of not only my group but also other groups here in Milan.