World Oncology Forum 2015

Biomarkers of cancer angioprevention for clinical studies

Dr Adriana Albini - Fondazione Multimedica Onlus, Milan, Italy

There are data, epidemiological data, that suggest that one third of cancers could be prevented, so they would not occur if one can change lifestyle, diet, exercise and many attitudes and obviously stop smoking and lower alcohol consumption. So therefore prevention is very important, maybe even more important than therapy to decrease the cancer burden in the world.

What is angiogenesis and, following from that, what is anti-angiogenesis?

I’ve always been studying what is not the tumour itself but the surrounding of the tumour. I have a friend in this field, which is microenvironment, who says that there is a body around the tumour. So this is the tumour microenvironment, it’s the sense, the healthy sense, of the body that somehow helps the tumour to grow. Angiogenesis is part of the microenvironment and it’s the strategy that a tumour has to recruit new blood vessels to bring nutrition, oxygen, nutrients, growth factors and also to disseminate around the body. So then the idea to use angiogenesis as a target for therapy, so blocking the vessels, which has been called by journalists suffocating the tumours or actually make the tumours hungry and starve and die, that has been very important in new therapies.

Our idea is that actually this angiogenic switch or angiogenesis occurs early so you have a small tumour and in order to grow it needs the new vessels. So if we can prevent the vessel recruitment by the tumour then the tumour would not be able to grow. So we coined this term angioprevention which means prevention of angiogenesis and we have been studying how to prevent the phenomenon.

Is this type of prevention for when a tumour has already developed?

This is actually a correct question in the fact that there is possibly a very small tumour. If there is a small tumour and actually the bodies of many people have the lower clones of transformed cells but they don’t become tumours, invasive, aggressive, metastatic, because they don’t interact with the microenvironment. So they stay silent, they are dormant, that was the definition. If they manage to grow blood vessels then they can develop. This is one aspect, obviously it’s the one we study. So if there is a very small tumour and we cut the blood supply then it probably can’t grow and metastasise. So this is prevention of very early, early, early stages of a tumour.

Have you identified biomarkers for this?

Actually we do try to prevent angiogenesis with diet derivatives, so a nutritional approach. There are many biomarkers for anti-angiogenesis, not as many as we would like but we can look at VGF levels which is the vascular growth factors, the major growth factor, which could be a marker but has not been completely proven. Or we can study metabolomics or circulating endothelial cells, a technique that’s been developed, for instance, by Bertolini at EIO. We are trying to study metabolites, for instance with people that have risk of cancer. We’ve done a recent publication with prostate cancer when you can look at people that have more markers at risk, for instance, and see if we can have that as early for monitoring them and prevention attitude.

Now the new kid in town for markers is the microbiome. In fact, we think that if you have a dietary approach also to prevention of angiogenesis then probably the intestinal microbes would change with time and that could become a marker of therapy. So this is a lot of new stuff but the marker field is still under development.

What is your lab looking into?

We’re looking particularly at some diet derived molecules, phytochemicals, aspirin also originates from a phytochemical which was from salicylic acid. Our favourite molecules are a beer derivative, beer hop derivative, called xanthohumol, and it’s like the resveratrol in wine, it’s a polyphenol antioxidant cancer preventive. Cancer preventing we have to prove with work on it. Also, for instance, a watery extract from the olive which would be a waste product, we do a collaboration with a group of producers of oil and this is very cheap polyphenols that get filtered, purified, then we do studies on cells; we do patents with that. We collaborate a lot with the Italian Association for Cancer Research which is very interested in the prevention approaches and particularly related to diet, dietary. It would be a waste product so it has also some environmental impact – instead of wasting we can recuperate it and concentrate. This little nutritional product that can be done has in one cup the content of polyphenols of half a kilo of olives so it can be a very good source of antioxidant polyphenols. Obviously we have to do the studies in cells, in vitro and then in preclinical models. Then later on we can do clinical trials.