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Attract to kill: Exploring the potential of motility trapping as a novel treatment strategy for high-grade gliomas
Anne-Sophie Bamelis1,2,3, Dennis Serge Metselaar4,5,6, Mariska Sie4
1Department of Neurosurgery, Ghent University Hospital, Ghent, Belgium.
Abstract:
High-grade gliomas (HGG) are notoriously hard to treat due to surgical limitations and resistance to systemic therapies, resulting in a dire prognosis. Tumor cell motility is a major contributor to treatment failure but simultaneously offers a therapeutic opportunity, utilizing a novel approach called "motility trapping". Motility trapping leverages chemotactic signals to redirect tumor cells to a location where local therapies can target them more effectively. This concept can be applied inward, drawing disseminated tumor cells back to the primary tumor, or outward, guiding them toward a more therapy-accessible location. While preclinical research demonstrates that motility trapping can influence tumor migration, clinical translation remains unestablished. To advance clinical applicability, 4 essential components must be considered: effective migratory stimuli, susceptible tumor cells, suitable delivery systems, and the influence of the tumor microenvironment. For each element, we review current knowledge and propose future directions to develop this innovative approach. In conclusion, redirecting HGG migration through motility trapping offers a transformative strategy that warrants further preclinical and translational investigation. It holds promise to synergize with a plethora of therapeutic strategies that are currently ineffective in brain tumors and should be considered in the design of future therapies.
Insights
Motility trapping redirects high-grade glioma (HGG) cells using chemotactic signals, offering a novel therapeutic strategy. This approach aims to improve treatment efficacy by guiding tumor cells to targeted therapy locations.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Translational Medicine
Background:
- High-grade gliomas (HGG) present significant treatment challenges due to surgical difficulty and therapy resistance.
- Tumor cell motility is a key factor in HGG treatment failure and recurrence.
- Current treatments for HGG have a poor prognosis.
Purpose of the Study:
- To explore the potential of
- motility trapping
- a novel therapeutic strategy for HGG.
- To review the essential components for clinical translation of motility trapping.
- To propose future research directions for advancing this approach.
Main Methods:
- Review of current preclinical research on motility trapping in HGG.
- Analysis of four critical components for clinical applicability: migratory stimuli, tumor cell susceptibility, delivery systems, and the tumor microenvironment.
- Identification of knowledge gaps and future research avenues.
Main Results:
- Preclinical studies show motility trapping can influence tumor cell migration.
- Clinical translation of motility trapping is currently unestablished.
- Key factors for successful implementation include effective stimuli, susceptible cells, appropriate delivery, and consideration of the tumor microenvironment.
Conclusions:
- Motility trapping presents a transformative strategy for redirecting HGG migration.
- Further preclinical and translational research is warranted to establish clinical applicability.
- This approach holds promise for synergistic effects with existing and novel brain tumor therapies.
