ASCO 2011 Annual Meeting, 3—7 June 2011, Chicago

Translational research from the Vall d’Hebron Institute of Oncology

Professor Joan Seoane – Vall d’Hebron Institute of Oncology, Barcelona, Spain

I’m the director of a research programme, it’s called translational research programme in the Vall d’Hebron Institute of Oncology. It’s a programme that is just beginning and we are waiting for a new building, the Cellex Building, to fill up this programme with scientists. We are very interested in linking the basic science with the clinical science and for that what we want to do is to set up models, models that study cancer as closely as possible to the patient. For example, what we do is we obtain samples from the patient, we isolate cells, we can study those cells in our lab and then translate the information of those cells to the patient that is undergoing, for example, clinical trials.

Not stem cell cultures?

Yes, we are doing those.

Including stem cell cultures?

Yes, we are doing what we call primary culture tumour cells, so that’s old cells, but also we are isolating these cells that have stem cell characteristics called cancerous stem cells, cancer initiating cells.

And mouse model systems?

Exactly, so what we do is we isolate those cells, we inoculate them in mice and they reproduce the characteristics of the tumour of the patient with the same genotype, meaning the same mutations, the same histology. And so what we can do is use those mice to test different compounds, see which is the compound that works the best and then this information translated to the patient to advise which is the clinical trial that can be best for him. Also we can isolate or we can study which are the markers, the biomarkers, that will predict which is the best compound to be treating this tumour.

Are you particularly interested in brain?

Yes, we are very interested in brain and this is one of the main focuses of our lab. We have all these systems made with brain tumours so what we do is we inoculate the cells in the brain of mice to reproduce the tumours.

Are you allowed to tell me if you’ve actually found a brain cancer stem cell or not?

Yes, we’ve found them.

What’s your marker? Because we’ve been looking at the so-called putative markers at the European Institute in Milan, as you know, and Giuliana Pelicci is not convinced that any of these actually hold water, if you know what I mean, if you test them. So what have you got to convince us?

Unfortunately, like in cancer, there is heterogeneity. We cannot say cancerous stem cells as a unique entity, there are different cancer stem cells depending on the tumour so that’s why there are different markers. But we have discovered and published last year in Cancer Cell is that in some subtypes of glioblastoma there are cancerous stem cells with CD44 expression, the same ones that Dr Weinburg was explaining in breast. So it seems that this entity might also be present in glioblastoma. Now that doesn’t mean that in other tumours there might be other cells with stem cell characteristics with other markers.

Do you think it’s a stem cell associated marker or is it a specific marker, CD44? I’ll tell you my bias after you’ve talked.

The thing is that unfortunately we don’t have good markers to really pinpoint and specifically find what is the cancerous stem cells, that’s why what we say normally is that this marker enriches for cancerous stem cells. So we have a population that is enriched in cancerous stem cells in the brain and this is CD44 highly one positive. So it has this other marker which is a transcription factor but we think it’s very important. The good thing is that functionally they act as cancerous stem cells, cancer initiating cells so we can isolate these cells and as few as 100 cells inoculated in the brain of mice, they generate tumours. So what we are doing in our lab is to study cancerous stem cells, the biology of them, find out which are the compounds that might be targeting these cells, but on the other side we’re using these mice that reproduce the tumour from the patient as a pre-clinical model to link, as much as possible, the basic research to the clinical research.

What are the candidate drugs in brain tumours, do you think, that are interesting?

Unfortunately right now there is not much and there is a lot of effort with different compounds, for example PI3K inhibitors or inhibitors of the PI3K pathway, EGFR, we are interested in, for example, notch inhibitors, TGF-β inhibitors, sonic hedgehog inhibitors, these types of inhibitors because we think that these inhibitors will also target cancerous stem cells.

And there are some of them available.

Yes, there are clinical trials.

And notch, for instance is certainly relevant in breast cancer stem cells and probably also lung cancer stem cells.

The good thing is that in our hospital we have several of these compounds in clinical trials, such as the notch inhibitor, PI3K inhibitors, TGF-β inhibitors. Our last work is about TGF-β inhibitors, we have found that TGF-β is important for these cancerous stem cells to self-renew, so if you inhibit TGF-β you have less cancerous stem cells.

And you are, of course, a very international institute, not just with your link to Mass General and obviously Baselga but you’re a member of the Organisation of European Cancer Institutes and you’re also one of the cancer institutes in the EuroCam platform FP7 project, which also we in Milan are in, and you’re hosting the European Association of Cancer Research meeting in Barcelona in July 2012.

Yes, 7th July 2012.

So 7th July, 2012, Barcelona, EACR. What are you going to put on for us?

We are going to try to get the best scientists in cancer research. Our subject, or the general subject or concept of the meeting is about personalised medicine, how to bring all the information that we have from basic science into how to stratify patients, classify patients, to find which is the perfect treatment for each patient with tumour characteristics.

All biology or molecular pathology, imaging?

What we want is this translational so basic and clinical, biology and clinical research getting together and synergising in some way. So we are having some of each, that’s why the personalised medicine – compounds, the characteristics of the tumour and getting them together.

Well ecancer.tv will be there on July 7th 2012 and thank you very much for coming and taking time out of the ASCO meeting; I’m sure that the EACR meeting will be probably a better meeting on translational science, and I look forward to that very much indeed.

Thank you very much, it is a pleasure to be here.

It’s nice to have you.