In the strategy of NICR, they were looking for a subject that would meet the parameters of both novelty and excellence. Václav Liška, head of the Laboratory of cancer treatment and tissue regeneration, which is active at the Faculty of Medicine of CU in Pilsen, was for these reasons attracted to rare tumours. In part because their research is not in an optimal shape, both because due to their rarity there are not enough samples and because it is not a ‘trendy’ subject.
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Your group focuses mainly on the clinical aspect of cancer research. What are the specific features of such work, for instance in terms of collaborating experts or institutions?
The main specific feature is contained in the very name of our group. ‘Laboratory of cancer treatment and tissue regeneration’ makes at first sight a somewhat incongruous impression. But both things are linked to growth. Tumour is uncontrolled growth, while regeneration, which leads to a functional renewal of tissue, is growth that is in some way controlled.
Within NICR, we cooperate mainly with the research teams of Professor Kari Hemminki and Professor Pavel Souček. Both represent the Faculty of Medicine of CU in Pilsen, as we do. They deal with solid tumours in the visceral area, such as colorectal carcinoma or carcinoma of the pancreas, but also some extra-abdominal one, such as kidney carcinomas or gynaecological tumours. We really enjoy collaborating with Professor Hemminki. We have managed to bring him here as part of the ERA Chair, Chaperon European project, thanks to which his laboratory could be created, acquire new researchers and PhD students, win grants, and hopefully successfully continue.
I have been working in cancer research for about 25 years, and the Biomedical Centre of the Faculty of Medicine of the CU in Pilsen has been in existence for the past ten years. Over that time, we have established countless research collaborations across research institutions and participated in many multilateral grants. Not all partnerships are formalised under the auspices of NICR. Many are established ad hoc for particular projects – and yet they work. I view many team leaders from other research groups as my regular collaborators and in effect do not think about the fact that they are from another institution.
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What oncological diseases do you focus on in your research and why?
We were looking in the NICR strategies for a topic that would meet the parameters of both novelty and excellence, a subject with which we could, in the future, apply for eventual European calls. Based on these considerations, we opted for the area of rare tumours, that is, tumours which are present in the population only in dozens or hundreds of cases and their research is not in an ideal shape. It is both because due to their rarity there is a shortage of samples and because it is simply not a trendy subject. That is why we chose to study neuroendocrine tumours and started working on it in collaboration with other teams. We should be able to publish something already next year, although on the other hand I believe that the subject is so interesting it would not be a good idea to exhaust it by just jotting something down quickly. It would be better to work on it properly and put together a publication for instance in the first decile journal.
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Your research group works on a large database of prospectively followed diseases and their clinical development in relation to treatment. What are your main expectations of this undertaking?
This database is unique in that we have been updating it since 2008 and we work with actual prospectively collected data. It should be borne in mind that all retrospective analyses, which include for instance pathological samples and retrospectively add some clinical data to them, tend to have a relatively high error margin. We are very proud of really collecting prospective data. Our database is not enormous: it includes about 1,000 or 1,200 patients, but one can find in it small homogeneous groups that can be easily studied because we have all the relevant data for those patients. One can thus define a particular clinical question and then, based on a concrete homogeneous group, search for an answer – and that is preferable to searching in some large highly varied datasets.
For instance, we wanted to find out what is the difference between primary intestinal tumours that metastasise into liver but not into the lymph nodes from those that do. For that, one must have patients who are followed over a long period of time and in whom only the first or the second variant of the disease had developed. Because we had samples collected over 8 or 10 years, we were able to selectively compare just 20 or 30 patients from each group. If we did not have such data, we would have to laboriously sift through the data of hundreds or thousands of patients. Such analysis would be much more time-consuming and naturally also more costly.
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Let us change the subject now a little bit. I have read in connection with your group that your research, undoubtedly because you specialise in surgery, extends also into post-operative complications, their solution and prevention by the development and use of innovative materials. What does it mean in concrete terms?
In this area, we cooperate with the ETH, that is, the Eidgenössische Technische Hochschule in Zurich, one of the most progressive technical schools in the world. In particular, we work with Professor Inge Hermann, whose laboratory concentrates on research and development of materials. What we are looking for are materials capable of addressing some concrete surgical need while being in some sense intelligent. To put it differently, they should be capable of reacting to some new situation and help either with the treatment or with the diagnostics.
What we started with were patches used for connecting the intestines after resection. Current materials can degrade over time, leading to a seepage of intestinal content into the abdominal cavity. We have therefore developed a material that would detect the rick of such leakage by a gradual change of its structure. We can then capture these changes by imaging methods during a checkup and react to them on time.
Another example of our research are materials that would, after tumour resection, alert us to an eventual local relapse or micro-metastatic spread. These need not be patches: it could be just a few grains of material that would in case of early progression change structure and in a horizon of weeks or a few months in an imaging examination draw our attention to early regrowth that would be visible by simple CT or magnetic resonance only after six or nine months.
This is the direction of our collaboration with the ETH in Zurich, and it is a really extensive effort: we have about twenty people participating on our side and certainly over twenty on the Swiss side. Moreover, we have managed to acquire for this cooperation an international bilateral grant of the Czech Science Foundation as part of the Weave European initiative.
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How promising is a better understanding of the principles of tissue regeneration and its use for the future of cancer treatments?
Research of tissue regeneration is our parallel subject. It is not part of the goals set within the NICR. We focus especially on the liver, which can be replaced after resection by a transplant, but it is not an option in all patients. Regarding research on liver regeneration, we have conducted an eight-year, i.e., relatively long experiment to verify the concept of de-cellularisation/re-cellularisation. We take some animal tissue, usually of porcine origin, and remove all cells in order to acquire an extracellular matrix. Then we try to populate by the cells of the recipient, thus in effect creating artificial liver. Another variant we have been working on is de-cellularisation of the tumour in situ together with the liver and subsequent re-cellularisation of the liver. It sounds a bit fantastic, but we have very good results in mouse models. That being said, it does not automatically mean that it is going to work in humans; for the moment being, we are just trying to investigate the mechanisms underlying this process.
People sometimes forget that the body can repair and heal relatively many things on its own. It is just about giving it the right kind of ‘push’ at the right moment. The regenerative capacity of the body is enormous; it’s just that so far, we do not understand it well enough.
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To what extent is the backing of a consortium such as the NICR important for modern research? Where do you see its contribution – and are you aware of things that should be improved?
NICR has a highly detailed strategy of support of cooperation in cancer research and its development. I personally see the greatest contribution in its ability to show how highly developed cancer research is in the Czech Republic, how firmly anchored it is here, and how many people are actually involved in it. This helps us to better communicate with the state authorities and puts us in a much better place in terms of acquiring support.
Science and research are a very delicate system. Just consider how long it takes to train a new scientist: five years of doctoral study (although many young researchers are active in our labs already during pre-graduate studies) but then it is the right time for the young researcher to go abroad and work for let’s say five years as a postdoc there. So, after ten or twelve years the young researcher becomes a self-sufficient scientist who is not only capable of educating the next generation but above all can acquire for them the means for research. And if some sort of crisis comes into it, there is no money … and this delicate, carefully built system suffers a blow that leaves a lasting impact. And I believe that NICR is in a position to stress that we need above all a stable environment in order to conduct cancer research in all the five research programmes it had defined as its goals.
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Btw, I found the motto of your group quite interesting. says: ‘Good research says why cancer happens and how cancer behavers. The best research tells us how to prevent cancer and how to treat it.’ How close are you to this best research? ☺
Once I was asked in an interview for a magazine whether I had some personal motto. I told them it is: In hoc signo vinces, meaning ‘In this sign, you will win’. This motto is written into the full coat of arms of Pilsen but its origins go back to the 4th century and outside the Czech Lands. It refers to the Roman emperor Constantine the Great, who saw the sign of cross before a battle – and he won. What I took from it is the message that if you stick firmly to your idea, you will win.
So, that’s my personal motto, but for our research group we naturally looked for something else, our own motto. There is about forty of us in the lab, so I asked quite a number of people. In the end, it was engineer Hošek – by the way a phenomenal statistician and bioinformatician – who came up with this motto. I think he managed to grasp very well what we do and what challenges we face. I do not know how close we are to the ‘best research’ but what is important is that we can keep looking at this motto and think about it. A good motto should be like a Baroque picture – one day you see it one way, the next day differently, and in ten year’s time, you can perhaps again see something completely new.
Recently, I have been going through the mottos of other NICR research groups and I must say they are really excellent. I would like to take some more time to think about them, because they reflect the philosophy, experiences, and impressions of many colleagues I know personally. I have a feeling that they will hide various deeper surprises and finding them would be the reward for taking the time to think about them…
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And finally, something a little personal: what do your colleagues from other groups in the NICR not know about you (and should know)? ☺
I have three children – mind you, with just one wife, because colleagues sometimes ask me whether I’m already ‘doing the second round’ ☺ And all of our family fell in love with the Bohemian Forest, where we spend all of our free time. For those who don’t know it there: the Bohemian Forest is not only the range on the Czech side but also in Bavaria. ‘Our’ Bohemian Forest is naturally beautiful, and one could keep discovering all life, but the Bavarian side has a completely different charm. It’s another aspect of the Bohemian Forest. It would make me happy if I could inspire someone here. One should not hesitate and just go discover wonderful places such as Großer Falkenstein, Großer Rachel, or Lusen.
