Migrastatics: a promising treatment
Metastasis is responsible for 90 percent of deaths in patients with solid tumours. So-called migrastatics will help to put an end to cancer cell invasions. The team surrounding biologist Jan Brábek is researching these new drugs.
It happened in 2017. At that time, the team from the cancer cell invasion laboratory at the Faculty of Science, Charles University came up with a unique concept for a new category of anti-cancer drugs. The substances, for which they gave the name migrastatics, are intended to prevent all forms of cancer cell invasion through the intercellular environment. Jan Brábek was awarded the Czech Brains (“Česká Hlava”) Award - the Invention Award (2019) for this completely new way of treating cancer patients. And today they are increasingly hopeful that migrastatics will reach patients in less than a decade.
In a pact with the IOCB and the Koreans
The migrastatic treatment proposed by Brábek is referred to as a new concept in the fight against oncological diseases. It is often referred to as the fifth pillar of treatment (the first to fourth pillars are surgery, chemotherapy, radiotherapy, and immunotherapy). Anti-tumour drugs based on the principle of migrastatics in combination with selected cytostatic drugs and other treatments could represent a promising approach for the treatment of metastases in the foreseeable future. "We are a cell-biological laboratory. In the development of new migrastatics, we therefore joined forces with synthetic and medical chemists, and we are working on synthesis with a number of domestic and foreign workplaces,” explains Brábek, who in 2015 anchored himself in Vestec at the BIOCEV centre.
The "partners" also include a group at the Institute of Organic Chemistry and Biochemistry of the Academy of Sciences, led by Pavel Majer. "They have succeeded in developing a substance entering the first phase of clinical trials: it prevents glutamine from entering cancer cells and thus suppresses growth. And in cooperation with us, they are developing drugs with a migrastatic effect," says the scientist. They also have other close colleagues in Pavla Perlíková's team at the Dejvice Institute, with Vladimír Kryštof from the Institute of Experimental Botany of the Czech Academy of Sciences in Olomouc, Pavel Martásek and Milan Jakubek also from Vestec and people at the University of Science and Technology in South Korea.
A promising substance, mitoDFO
At present, experts are studying several substances which appear to be very promising in preclinical testing. “Among them is mitochondrially targeted deferoxamine – mitoDFO, which targets mitochondrial iron metabolism: it takes advantage of the fact that tumour cells need more iron, and it prevents further tumour growth by blocking iron metabolism," says the biologist. The purely Czech research, which was discussed in April by Cancer Research, is, among other things, being conducted at the Laboratory of Tumour Resistance of the Institute of Biotechnology of the Czech Academy of Sciences, headed by Jaroslav Truksa, and Smart Brain s.r.o., which has long supported promising scientific projects.
“In our research, we found that mitoDFO is a potent inhibitor of cancer cell migration and invasiveness. Migrastatic effects in 3D models have subsequently been reflected in a strong anti-metastatic effect of the molecule in an animal model. It will be up to the colleagues how quickly they are able to introduce this promising molecule into clinical studies," reveals Associate Professor Brábek, who is proud that the research is a prime example of connecting individual expertise at the centre: "Our laboratory is cooperating with colleagues from the Institute of Biotechnology of the Academy of Sciences in several projects linking cancer metabolism and cancer cell invasiveness."
As soon as possible to patients
Under optimal conditions, testing substances in clinical trials takes ten to twelve years, with development costs of nearly $1 billion each. But researchers would like to get migrastatics to patients sooner. "The shortest way is to use innovative, already approved drugs. That is why we have recently started testing them for anti-invasive and anti-metastatic effects," reveals the associate professor. To test existing drugs, his laboratory has teamed up with a number of experts and clinical oncologists, often from a number of workplaces at the 1st FM CU.
In addition, any new formulation of already approved medicines makes it possible to apply for patent protection in the European Union and the United States. "This is also a commercially interesting area with great potential for pharmaceutical companies that might be interested in testing these substances. Migrastatics could thus reach patients much faster," believes Brábek, who aspires to become a professor.
Greatness under one roof
In addition to Associate Professors Jan Brábek and Daniel Rösel, the laboratory team consists of three postdoctoral students, four postgraduate, four undergraduate students and a laboratory assistant. For university conditions, it is more of a larger laboratory. The advantage of new infrastructures, such as BIOCEV, is the close cooperation between CU and the Academy of Sciences.
"The common instruments and expert background are exceptional, which is also admired by scientists who come to us from Western Europe or the USA. Here you will find all types of super-resolution microscopy, excellent mass spectrometers, the Czech Centre for Phenogenomics and moreover - researchers work well together within the centre. In short, it is the ideal setting for good science," as Jan Brábek answers the question of how science is done in the Czech Republic. And with a little relief and a smile, he adds: "Conditions today are not very different from the most developed countries in the world. What could also help university research in particular would be stable, higher institutional funding for groups that are able to deliver quality scientific outcomes in the long term."
Doc. RNDr. Jan Brábek, Ph.D., leads the Molecular and Cellular Mechanisms of Invasiveness of Tumour Cells group at the BIOCEV centre. He graduated from the Department of Cell Biology, Faculty of Science, Charles University. In 2005, after returning from a "postdoc" at Vanderbilt University in the USA, he and Daniel Rösel founded a laboratory to study the invasiveness of tumour cells at the faculty. Since 2019, he has been testing substances with migrastatic effects. He is a laureate of the Czech Brains - the Invention Award, the Bedřich Hrozný Award and has been awarded twice by the League Against Cancer for important publications in the field. When he is not in the laboratory or is not reading (or during the pandemic he was not supervising the education of his two sons), we can see him in Krč Forest, where he practices the eastern martial art of Sing and Chuan.
Source: Forum 2/2021, Magazine of the Charles University
Text: Marcela Uhlíková
Photo: Michal Novotný