Malignant primary and secondary brain tumors are among the most lethal human cancers, with glioblastoma IDH-wildtype (GB) being the most aggressive and frequently occurring. GB has a median survival of only 8 months, with a 5-year survival rate of 6.9%. Standard treatment for GB includes microsurgical tumor resection, radiotherapy, and concurrent chemotherapy with temozolomide. Achieving gross total resection is critical to improving progression-free and overall survival. However, despite advances in microsurgery and fluorescence-guided resections with agents like 5-aminolevulinic acid (5-ALA), only about half of cases achieve macroscopic gross total resection. This difficulty is largely due to tumor location in functional brain areas, which complicates safe removal without neurological risk, as well as the infiltrative nature of GB, which often extends beyond MRI-visible areas. Even with aggressive treatment, chemoradiation struggles to eliminate residual, resistant GB cells, leading to frequent recurrence at the resection site. In fact, 85% of GB patients experience tumor recurrence at the margin of the resection cavity within months post-surgery.
Although extensive research has been devoted to understanding the complex heterogeneity of GB, the peritumoral region where recurrence occurs has not been adequately characterized in the early post-operative period. Additionally, while surgery remains a cornerstone of GB treatment, its effects on cellular plasticity and the surrounding tumor ecosystem are not fully understood, largely due to the absence of reliable, reproducible models for studying these processes.
