Spatial-in-Spatial: The Utility of Combining Fluorescence-Guided Multiple Sampling with Spatial-Omics in Human...

Human glioblastoma (GBM) is a remarkable example of a highly aggressive and untreatable tumor. A formidable challenge in treating GBM is its extensive intratumor heterogeneity, which traditional bulk tissue analysis fails to capture. Fluorescence-guided multiple sampling, utilizing 5-aminolevulinic acid for tumor visualization, offers objective tumor tissue identification and enhanced spatial resolution. In this study, we present a perspective on a novel "spatial-in-spatial" approach that enables comprehensive analysis of tumor areas and their microenvironment-at macroscopic and microscopic levels-by combining fluorescence-guided multiple sampling with spatial-omics technologies. This perspective discusses how this integrated methodology has the potential to advance our understanding of GBM biology through the high-resolution, multidimensional characterization of tumor heterogeneity and identification of novel, area-specific therapeutic targets.