8. Jan. 2020

This year, the committee of the League Against Cancer Prague awarded two awards for significant achievements that were published in 2018 in the field of Oncology – one for Associate Professor Marek Mraz from the University Hospital Brno and Research Group Leader at CEITEC Masaryk University, and the second one for David Vrana, Head of the Comprehensive Oncology Centre of Novy Jicin Hospital.

Associate Professor Marek Mraz studies blood cancers, especially chronic lymphocytic leukaemia and B cell lymphomas, and the possibilities of their treatment. His main workplaces are the Department of Internal medicine, Haematology and Oncology at the University Hospital Brno, and CEITEC at Masaryk University in Brno, where he leads a research group. He conducted post-doctoral work in the United States, and received multiple scientific awards. He published more than 40 scientific papers and obtained a patent for a method used to predict the response of patients to therapy. This year, he was awarded by the President of the Czech Science Foundation (GACR) for the best project funded by this agency.

Editor of The Cancer League's bulletin, Iveta Kuchařová, asked Dr. Mraz if he would answer a few questions:

What is the main focus of your work?

I study the biology and targeted therapy of diseases called B cell malignancies i.e. B cell lymphomas and leukaemia. Most of the work that my team and I do is devoted to research on chronic lymphocytic leukaemia (CLL), which is the most common leukaemia in adults. The development of this particular disease, unlike many other forms of leukaemia, is still unclear, and most importantly, is also incurable (with the exception of haematopoietic stem cell transplantation). To be precise, it is difficult to completely and permanently control CLL in patients. We are working on several projects that examine this disease from various perspectives - from very basic molecular biology questions regarding the development of this disease, to projects where we actively search for effective targeted treatment, as well as the development of animal models of this and related diseases. In the last few years, we have managed to describe new mechanisms regulating the so-called BCR signaling pathway, which is probably the most important pathway affecting the onset and aggressiveness of most B cell malignancies. This pathway is also an excellent therapeutic target. We strive to ensure that these discoveries will also lead to the development of new drugs, clinical trials, or their improved variants.  

Did your family influence your choice of profession?

I was fundamentally influenced by both of my parents, who always greatly supported my interest in nature during my childhood. However, I would say that my interest in nature as such evolved somehow independently. It's hard to say what actually determines that someone is interested in nature, another in machines, and someone else in the arts. I also knew from an early age that I was not fascinated that much by plants…What I do specifically in research today was largely influenced by the excellent scientists and doctors that I met during my studies at university (mainly Professors Jiri Mayer, Sarka Pospisilova, and Alois Kozubik, as well as Associate Professor Martin Trbusek).

You studied molecular biology and medicine at the same time. What led you to study both disciplines simultaneously?

Partially, indecision. I couldn't imagine empirically treating patients without really understanding the molecular nature of their diseases. During my studies, the main therapeutic strategy in oncology was classical chemotherapy (besides surgery and radiotherapy). Targeted treatment with small molecules or antibodies was used very rarely. At the same time, I could not imagine that I should study cancer cells only in a laboratory, without any contact with clinical medicine. Moreover, once I started studying medicine, it was impossible not to continue, because the study gave me a glimpse into how my own body works, which in itself was motivating enough. Actually, I can't even imagine living my entire life without that knowledge.

How long did you work in the United States, and how has this experience affected you?

I worked at the Mayo Clinic for a year, and then several years at the University of San Diego (California). I learned how to lead a scientific team, how to be scientifically determined and to not give up, to try things differently, and that failed experiments are the norm. I've also seen that even the most talented people with the best education in the world have to work hard to succeed and to discover something truly interesting. In addition, I met several colleagues there who became my lifelong professional mentors, as well as personal friends, and I always look forward to meeting them at scientific conferences. We have a great dynamic because on one hand, we "compete" with each other, and at the same time, we are all solving scientific issues and cooperate and respect each other. Through science, I am connected with people from all over the world, because I could have a long discussion with a scientist I met for the first time about our common scientific interests.

Can one’s personal life be combined with such a time-consuming profession?

We have a little baby girl at home, so this question is real for me now. So far, we're managing…(probably). Science is a profession that I do for a living, and at the same time, it is my greatest hobby. I have never done anything that fascinating (not even close), and it is in fact hard for me to imagine that something more fascinating even exists. When we discover something, and it helps patients, I feel like life somehow makes sense. It takes a huge amount of time, and I dare to say that a large proportion of scientists don't really know (or don´t want to know) how to stop thinking about work. Therefore, they tend to work all the time. However, combining science with personal life is certainly possible, and there are also excellent scientists who work 8 hours a day and don't even think about the lab during the weekend (but I'm not one of them).    

How does current oncology benefit from your research?

My laboratories at the University Hospital Brno and CEITEC Masaryk University are dedicated to understanding the mechanisms that govern the survival and proliferation of malignant B lymphocytes in the previously mentioned B cell malignancies. We have described several so-called non-coding RNAs that control the BCR signalling pathway, which resulted in the creation of a new drug, which is now in clinical testing. We also described that a molecule on the surface of cancer cells called CD20 is involved in the same BCR signaling pathway. Its levels are controlled in a very sophisticated way, so that in some context, this molecule will allow malignant B cells to activate this pathway. This impacts the combination treatment of so-called anti-CD20 monoclonal antibodies, such as rituximab, with other drugs. Our discovery also influenced the way in which these clinical trials are now being designed. Our work has led to several patents, and at the moment, we are working on a novel treatment strategy for B cell leukaemia and lymphomas.  Currently, we do a lot of applied science, but this was preceded by several years of completely basic research. In general, I believe that it is a major mistake that some institutions currently intend to support applied research more, at the expense of basic research. For example, current progress in the treatment of cancers is based on a fundamental understanding of the mechanisms of development and progression of these diseases at the molecular level. Thus, this allows the laboratory testing of targeted treatments, the development of targeted drugs, clinical studies, and ultimately the common usage of highly effective therapeutic strategies that dramatically change patients' prospects. Without basic research, we would still be "trapped" in the empirical circle, testing some form of chemotherapy on large groups of patients with seemingly the same cancer, which would not lead to significant improvement in therapy in most tumour types (probably with a few exceptions).

Author: Iveta Kucharova

Source: League Against Cancer Prague


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