Scientists from the Michal Masařík Research Group are contributing to the development of migrastatics – drugs that limit the movement of tumour cells, thereby reducing the risk of metastasis formation. Using them, they are developing a new concept of antitumour therapy.
Surgery, radiotherapy, chemotherapy. Only in exceptional cases do doctors in the treatment of oncological diseases rely on just one of these methods. Usually they resort to their combination. The idea that one could similarly amplify the effect of therapy already at the level of the drug itself, Czech scientists are also considering. Among them are those from the Michal Masařík Research Group, operating at the Institute of Pathological Physiology of the Faculty of Medicine at Masaryk University.
Block, reveal, destroy – this is also how one can figuratively translate the apt title and after all the therapeutic procedure whose concept was published by the prestigious journal Trends in Molecular Medicine. “We propose a combination of migrastatics, which restrict the movement of tumour cells and thus their spread, photodynamic therapy, which selectively kills them, and intratumoural immunotherapy, which prevents the tumour from coming back,” names Professor Masařík the basic pillars of the presented approach. Although the text takes the form of a so-called opinion piece, whose purpose is to stimulate other scientists – and in this case also doctors – to discussion and commentary, as Michal Masařík emphasizes, it is not just theory: “We already have practical data from verified experiments with specific compounds that we know work for our concept, albeit so far only at the in vitro level and in mouse models.”
The idea of a “triple attack against cancer” arose thanks to the collaboration of scientists from several research institutions. The impetus was the internship of engineer Kateřina Hönigová, a doctoral student from Michal Masařík’s team, who at the U.S. National Institutes of Health (NIH) in Bethesda gained experience alongside Professor Karel Pacák, a world-renowned expert in the field of endocrine oncology. Scientists from the team of Associate Professor Milan Jakubek at the First Faculty of Medicine of Charles University also participated in the development of the innovative concept, and the topic of migrastatics has been developed long-term also by experts from the Faculty of Science of Charles University, specifically the team of molecular and cellular biologists from the BIOCEV research centre under the leadership of Professor Jan Brábek.
Jan Brábek was already in 2020 awarded the Česká hlava prize for defining migrastatics as a new category of antitumour drugs that prevent tumour cells from moving, and thus forming metastases. While the primary tumour is in many cases operable, it is precisely metastases that are responsible for up to ninety percent of oncological patient deaths. “A tumour arises from a cell that changes its phenotype, loses control over its division and begins to divide uncontrollably. However, once this primary tumour grows to a certain size, it begins to spread and form metastases, which are often phenotypically different from the primary tumour,” describes the process of disease development Michal Masařík.
“Probably no therapy can be used universally and it is always good to target several key features of tumour cells. That is why we propose how these three approaches could hypothetically work in synergy and how they could complement each other,”
Kateřina Hönigová
Establishing a metastasis is not easy for a tumour cell. In order to survive the journey through the bloodstream or lymphatic vessels, it must change its phenotype and then find an energetically favourable site where it can survive and begin to grow. Once, however, it does happen and the tumour establishes secondary loci, treatment options become dramatically more difficult. And although the concept of preventing tumour cells from moving is not entirely new, it has only been developed in recent years. “A range of commonly used antitumour drugs such as cisplatin affect, for example, cell stiffness, which also influences their movement. But science only turned its attention to migrastatics as specific compounds that prevent cells from moving relatively recently,” says Masařík. Moreover, although specifically cisplatin has migrastatic potential, at higher concentrations it is already toxic not only to tumour cells but also to healthy ones, which in patients can manifest a number of adverse side-effects.
The principle of migrastatic therapy, on the other hand, lies only in restraining tumour cells within the tumour, not killing them by exposure to cytotoxic stress, which can negatively affect healthy surrounding cells as well. Suitable candidates for migrastatic drugs can also be sought among drugs already officially approved for the treatment of other diseases. Among them is, for example, metformin – a diabetes drug for which migrastatic effects have already been proven in the past, especially when used in the early stage of the disease. “That supports its potential for new use. And because it has already undergone testing and screening, it would be easier to get it to patients,” notes Kateřina Hönigová, according to whom migrastatic therapy alone may find potential application, for example, just before surgical procedures associated with the risk of tumour cell release into the bloodstream. But by itself it will not reduce or destroy the tumour.
That is why scientists propose a concept in which migrastatic therapy is complemented by the other two pillars – photodynamic therapy and intratumoural immunotherapy. “Probably no therapy can be used universally and it is always good to target several key features of tumour cells. That is why we propose how these three approaches could hypothetically work in synergy and how they could complement each other,” says Hönigová, adding that each of them faces its own challenges in development. “Photodynamic therapy is today certainly further on than the migrastatic one. Drugs such as the commercial preparation Photofrin are already approved and used, for example, in skin tumours or head and neck tumours. Likewise, several intratumoural drugs are in clinical testing phases.”
Scientists are also focusing on finding such compounds that would be capable of merging at least two approaches, with the lowest risk of side-effects for the patient. In cooperation with medicinal chemists from the First Faculty of Medicine of Charles University they are thus testing in Brno at the workplace of Masaryk University structures that have both a migrastatic effect and in which photosensitisers are integrated, thus making them capable of acting also as photosensitisers, i.e., substances activated by the action of light, capable of directly killing tumour cells. The advantage is that these substances respond to light of a certain wavelength and are active only locally, at the illuminated site. They are therefore not toxic to their surroundings and to healthy cells.
Similarly locally functioning is also the third pillar of the proposed therapeutic concept: intratumoural immunotherapy, which is intended to support the local immune response and, in the wider context, the entire immune system through maintaining memory cells, which prevent recurrence, that is the tumour returning. “If the tumour returns in the form of recurrent cells, then a therapy that worked on the original tumour often no longer works on these recurrent cells,” explains the importance of maintaining and strengthening immune memory Kateřina Hönigová. “On the contrary, it has already been tested in mice that if the immune system’s memory was sufficiently strengthened by a specific type of intratumoural immunotherapy, then in individuals to whom tumours were applied again, they did not grow any more.”
As Michal Masařík reminds us, scientists no longer rely only on theoretical data but also on a range of experimentally confirmed studies, including toxicity studies of the tested compounds. Thanks to the grant project of the Czech Science Foundation they can currently focus on describing the detailed effect of new methinium salt derivatives, whose newly discovered migrastatic potential they are testing, and further develop the “triple attack” concept. “It is a puzzle that is beginning to gradually take shape,” says Hönigová and welcomes the broader interest of the scientific community, thanks to which research in the area of migrastatics is being developed. “The U.S. Food and Drug Administration approved a few years ago metastasis-free survival as a primary endpoint in clinical trials focused on prostate carcinoma. That means that in the tested drugs today they evaluate also how much they can prevent metastatic spread. Thanks to that, migrastatic therapy may be advanced in development and approval of drugs. It is a big success that the community engaged in the development of experimental migrastatic drugs has managed to achieve.” And so let us just add: with no small contribution from Czech scientists…
The charity collection "Christmas Baking in the Campus," which took place on Monday, December 8, 2025, in the southern corridors of the Campus of the Faculty of Medicine and Faculty of Science at Masaryk University, successfully attracted students and staff. A pleasant Advent atmosphere prevailed throughout the day, complemented by the aroma of Christmas cookies and homemade sweet treats.
