Spatiotemporal Insights into Glioma Oncostream Dynamics: Unraveling Formation, Stability, and Disassembly Pathways

Glioblastoma (GBM) remains a challenge in Neuro‐oncology, with a poor prognosis showing only a 5% survival rate beyond two years. This is primarily due to its aggressiveness and intra‐tumoral heterogeneity, which limits complete surgical resection and reduces the efficacy of existing treatments. The existence of oncostreams—neuropathological structures comprising aligned spindle‐like cells from both tumor and non‐tumor origins‐ is discovered earlier. Oncostreams are closely linked to glioma aggressiveness and facilitate the spread into adjacent healthy brain tissue. A unique molecular signature intrinsic to oncostreams, with overexpression of key genes (i.e., COL1A1, ACTA2) that drive the tumor's mesenchymal transition and malignancy is also identified. Pre‐clinical studies on genetically engineered mouse models demonstrated that COL1A1 inhibition disrupts oncostreams, modifies TME, reduces mesenchymal gene expression, and extends survival. An in vitro model using GFP+ NPA cells to investigate how various treatments affect oncostream dynamics is developed. Analysis showed that factors such as cell density, morphology, neurotransmitter agonists, calcium chelators, and cytoskeleton‐targeting drugs influence oncostream formation. This data illuminate the patterns of glioma migration and suggest anti‐invasion strategies that can improve GBM patient outcomes when combined with traditional therapies. This work highlights the potential of targeting oncostreams to control glioma invasion and enhance treatment efficacy. The manuscript presents in‐depth studies on oncostreams, neuropathological structures involved in glioma malignancy and invasion. By developing an innovative in vitro model, the researchers revealed significant insights concerning mechanisms driving oncostream organization, invasion, and migration. Using specific pharmacological agents, they identified novel therapeutic strategies to advance the understanding of glioma cell behavior and potential anti‐invasion treatment targets.