Attract to kill: Exploring the potential of motility trapping as a novel treatment strategy for high-grade gliomas.

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.