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Halt migration – a new way of cancer treatment?

Cellular migration is crucial for the formation of metastasis – distant cancer cell deposits. However, metastasis is what makes cancer deadly in most cases. Prevention of their formation could thus present a promising approach to the treatment of the feared disease. The current options as well as prospects for the future are reviewed in a new paper by a scientific team joined by Jan Brábek and Daniel Rosel from the Faculty of Science, Charles University.

Migration and settlement of cancer cells outside of the primary tumor give rise to metastasis, which turns a localised tumor into a life-threatening systemic disease. Cells can migrate on their own or collectively. However, all the options require more energy, in the form of ATP, than usual. ATP is turned into mechanical force, which the cells use to make their way through the extracelullar matrix. Although each mode of migration is different, some factors are common to all of them – the increased need for energy, changed cytoskeletal dynamics and mitochondrial metabolism. These are the factors that migrastatic therapy is trying to target.

Cell migrate into the bloodstream and then out of it to give rise to distant metastasis.
author: Jane Hurd, source: Wikipedia


The cytoskeleton is, among others, formed from actin fillaments. However, targeting directly the fillaments is complicated as the exact same actin fillaments are found in our own healthy cells. If the dosing is not right, the drug cannot discriminate and it destroys all of them. Even some of the widely used cytostatic drugs are able to influence the cytoskeleton and thus prevent the formation of metastasis. One of those is the pioneer of organometallic cancer drugs – cisplatin. Interestingly, its migrastatic effect arises at lower doses than those needed for the cytostatic effect. However, the effect of cisplatin is still dependent on the type of tumor and the migration of some types is even supported by cisplatin. More, essentially non-toxic migrastatic drugs influencing the cytoskeleton are currently in various stages of pre-clinical testing.

As many of you probably remember from school, the mitochondrion is „the powerhouse of the cell“. Mitochondria produce the universal energetical currency of the cell – the ATP (adenosintriphosphate). Disrupting the electron transport chain which is key for ATP production could be another way of migrastatic therapy. Among the drugs that can interfere with it, is for example mitochondrially targeted tamoxifen, otherwise widely used drug for some types of breast cancer. Migrastatic effects could widen its use even more. One of the other options may come as a bit of surprise – arsenic oxide, previously used in grazing. Ingesting even microscopic amounts can kill immediately but an intravenous application may serve as a very good migrastatic and is even used for the treatment of acute promyelocytic leukemia. However, even the mitochondrially targeted drugs have their downgrades. Cancer cells are very flexible and they can import healthy mitochondria from nearby cells through so-called tunneling nanotubes to replace the damaged mitochondria.

Illustrative picture of mitochondrion.
source: Dalle-2


The problem of migrastatic therapy is the evaluation of its effect. It is a preventative treatment and its results are hard to visualize. The drugs don´t have to impact the commonly studied characteristics such as the growth and division of cancer cells or the size of the tumor. This can result in migrastatic drugs being misinterpreted as useless. To correctly evaluate the effect of the therapy, it is needed to study the number of new metastasis or how fast are they forming.

The future of migrastatic therapy is bright. It could present an effective tool for the treatment of cancer, and even if that’s not the case, migrastatics could at least enable lowering the dosage of common cytostatic drugs. The synergy of those two methods could thus limit the dangers of aggressive cytostatic drugs. Many malignant tumors could also be turned into chronic diseases by the use of migrastatics. Even though the migrastatic therapy is still in the beginning, it will be interesting to see how it evolves.

Magda Křelinová

Raudenská, M.; Petrláková, K.; Juriňáková, T.; Leischner Fialová, J.; Fojtů, M.; Jakubek, M.; Rösel, D.; Brábek, J.; Masařík, M. Engine Shutdown: Migrastatic Strategies and Prevention of Metastases. Trends in Cancer 2023, 9 (4), 293–308. https://doi.org/10.1016/j.trecan.2023.01.001.

Published: Jul 16, 2023 02:30 PM

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