Regulation of self-renewal in cancer stem cells

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Published: 20 Nov 2012
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Prof Pier Giuseppe Pelicci – European Institute of Oncology, Milan, Italy

As cancer stem cells support tumour growth, this makes them the target for therapies in order to prevent spread and relapse. Prof Pelicci talks about his presentation at the IFOM-Kyoto University Joint Symposium in Milan about the investigation of more targeted therapy looking at molecular functions.

 

Prof Pelicci’s primary research involves molecular mapping of Shc to find these targets and understand the mechanisms of resistance. 

Cancer stem cells are supposed to be the only cells which are able to support tumour growth so they are the target. As we know, the majority of the available treatment easily induces apparent cancer remission then the cancer will eventually relapse and that’s due to the persistence of rare cells. Those cells, by definition, are tumorigenic so they should be cancer stem cells. So if the hypothesis of cancer stem calls is true then the drugs that we have generated are not cancer stem cell specific. So we may have targeted the wrong cells. I don’t think we can sleep until we know whether this hypothesis is true or not.

So you’re looking to bypass conventional therapy for more targeted therapy?

Against the cancer stem cells, and to do that we have a big limit that we don’t know which are the cancer stem cell specific molecular mechanisms underlying their function so we don’t know exactly what should we target. That’s why it’s very important, that’s my main scientific interest, to map molecular circuits of cancer stem cells to identify hills where we can put our .

Will it be easier to define cancer stem cells in the future?

That is the strength of the cancer stem cell field because we discovered them through the transplantation but it’s also the big limit and we have to bypass it. I think that what we should do now is to ask the specific questions which are the cells that regrowth in tumours after tumour shrinkage within the context of the tumour itself, not outside as it is in the transplantation setting. This is one of the major avenues of research in general, including my lab.

Do you feel the neoadjuvant setting is a strong model?

I think that, as a matter of fact, the neoadjuvant setting is the best setting to test new drugs and to test mechanisms. As you mentioned there you have the unique opportunity to study tumours prior and after treatment and if there is a tumour after treatment to understand what is the mechanism of resistance. So I agree with you, we should potentiate those types of studies, ask the help of surgeons to collect samples, pathologists to categorise the samples and having the material to ask these types of questions.

What other research is there ongoing at the IEO?

Yes, it is interesting. The fact that you asked why are you interested as an MD and then basically you are asking what is the interest as a PhD. The major thing, and I think this should be thought as a motive, is that there is now contradictions because we can answer questions as an MD starting from fundamental questions and the fundamental questions here are very clear: how self-renewal of stem cells is regulated. Stem cells divide either symmetrically or asymmetrically, which are the molecular machinery? How does p53 regulate the symmetric versus the asymmetric division? Which are the targets? Which are the biochemical and biological mechanisms? These are fundamental questions so as a PhD it’s even more interesting if possible.