Atypical behavior of recurrent glioblastoma tumor cells with a highly adherent radial glial phenotype

Glioblastoma (GBM) is the most common malignant primary brain tumor, characterized by a high recurrence rate despite aggressive therapy. We present a case of a 32-year-old male with a recurrent WHO Grade IV IDH1-mutant astrocytoma after undergoing standard Stupp protocol chemoradiation and tumor-treating field therapy. Repeat surgery was performed where in vitro analysis of recurrent GBM cells revealed atypical behavior, rapid adhesion within minutes of plating, and the formation of radial glial-like cells (RGCs) with 3D aggregated cells, phenotypes absent in the primary tumor. These brain lipid-binding protein positive RGCs exhibited elongated processes that facilitated cancer cell migration, potentially contributing to tumor invasiveness. Extensive treatment between the primary and recurrent tumors may have induced this phenotypic shift, highlighting therapy-induced plasticity as a key factor in recurrence. The emergence of RGCs in recurrent GBM underscores the need for targeted therapies addressing tumor adaptability to improve treatment outcomes.