Abstract 3961: Identifying the molecular signature of infiltrating edge cells in glioblastoma as drivers of tumour invasion and recurrence

Abstract Glioblastoma (GBM) is the most common malignant brain tumor in adults. Despite extensive research, there haven’t been remarkable gains in resolving the seeds of GBM recurrence, and the outcomes for many patients suffering from this devastating disease remain poor. Our knowledge on GBM heterogeneity is mostly restricted to the surgically resectable tumor core, while functional characterization of tumor cells at the infiltrating edge remains largely elusive due to the presence of normal functional brain tissue in the peritumoral lesion. Edge-derived cells exhibit larger capacity for infiltrative expansion and are the main drivers of treatment failure and tumor recurrence, making them action targets for novel treatment approaches.In this study, we present a first-of-its-kind integrative spatial investigation of GBM, combining two complementary spatial omics modalities high-definition spatial transcriptomics (ST - Visium HD) and spatial proteomics (SP - COMET) to achieve a comprehensive morphological, transcriptomic, and proteomic characterization of invasive tumor edge in situ. This multimodal spatial framework enabled to resolve the complex molecular landscape of the GBM periphery and to identify druggable biomarkers specific to edge-derived malignant cell populations.By integrating pathologically annotated H Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3961.