Dissecting Intra-tumor Heterogeneity in the Glioblastoma Microenvironment Using Fluorescence-Guided Multiple Sampling

The treatment of the most aggressive primary brain tumor in adults, glioblastoma (GBM), is challenging due to its heteroge-neous nature, invasive potential, and poor response to chemo-and radiotherapy. As a result, GBM inevitably recurs and only a few patients survive 5 years post-diagnosis. GBM is characterized by extensive phenotypic and genetic heterogeneity, creating a diversified genetic landscape and a network of biological inter-actions between subclones, ultimately promoting tumor growth and therapeutic resistance. This includes spatial and temporal changes in the tumor microenvironment, which influence cellu-lar and molecular programs in GBM and therapeutic responses. However, dissecting phenotypic and genetic heterogeneity at spatial and temporal levels is extremely challenging, and the dynamics of the GBM microenvironment cannot be captured by analysis of a single tumor sample. In this review, we discuss the current research on GBM heterogeneity, in particular, the utility and potential applications of fluorescence-guided multiple sam-pling to dissect phenotypic and genetic intra-tumor heterogene-ity in the GBM microenvironment, identify tumor and non -tumor cell interactions and novel therapeutic targets in areas that are key for tumor growth and recurrence, and improve the molecular classification of GBM.

Automated summary

The treatment of glioblastoma (GBM), the most aggressive primary brain tumor in adults, is difficult due to its heterogeneous nature, invasive potential, and poor response to therapy. GBM is characterized by extensive phenotypic and genetic heterogeneity, which promote tumor growth and resistance to treatment. Dissecting this heterogeneity is challenging, and current research focuses on the use of fluorescence-guided multiple sampling to understand GBM microenvironment and identify potential therapeutic targets.