Intra-tumoral heterogeneity in glioblastoma is a critical factor influencing treatment resistance and disease progression. Recent studies have employed advanced methodologies to elucidate the complex molecular landscape of glioblastoma. For instance, one study utilized mass spectrometry to analyze the proteomic profiles of glioblastoma across 20 patients, identifying 4,794 proteins and proposing a triple-axis model of heterogeneity that reflects distinct histomorphologic niches within the tumor. This research highlights the importance of understanding regional variations in protein expression, which may contribute to differential responses to therapies (ref: Lam doi.org/10.1038/s41467-021-27667-w/). Furthermore, the study underscores the necessity of integrating proteomic data with transcriptomic insights to form a comprehensive view of glioblastoma biology. Another significant aspect of intra-tumoral heterogeneity is the spatial immune landscape within high-grade gliomas (HGG). A study focusing on the immune microenvironment revealed that the tumor core and peripheral regions exhibit distinct biological features, particularly in the context of hypoxia-induced immune exhaustion. By analyzing infiltrating immune cells and conducting RNA-seq on samples from 34 patients, researchers demonstrated that the immune response varies significantly between these regions, suggesting that therapeutic strategies may need to be tailored based on the spatial characteristics of the tumor (ref: Kim doi.org/10.1080/2162402X.2022.2026019/). This finding emphasizes the complexity of glioblastoma as a heterogeneous entity and the need for personalized approaches in treatment.