Tailoring imaging probes for defining glioma invasive margins: Tracing the molecular footprints of cancer cells.

Maximal safe surgical resection remains the cornerstone of glioma treatment, yet the infiltrative nature of this most common malignant brain tumor poses major challenges in accurately delineating tumor margins while preserving adjacent functional tissues. Addressing this limitation requires the identification of reliable invasion biomarkers and the development of highly specific materials to enable complete resection of diffuse glioma. This review explores the infiltrative growth patterns of glioma and classifies margin-associated biomarkers into three major categorizes: molecular, cellular and structural abnormities. Particular emphasis is placed on molecular and functional biomarkers, which often manifest earlier and more faithfully reflect cancer cell distribution than structural markers. We also highlight recent advancements in engineering materials and probes capable of detecting these abnormalities beyond the reach of conventional diagnostic tools, thereby enhancing intraoperative precision. Finally, we outline future perspectives for refining biomarker discovery and probe design to facilitate maximal safe resection. By advancing next-generation technologies for delineating diffuse glioma margins, these efforts hold promise for improving surgical outcomes and patient survival.