Asian Oncology Research Journal

Gliomas represent some of the most biologically heterogeneous and therapeutically recalcitrant primary brain tumours in human oncology. Despite decades of intensive research effort, the molecular mechanisms underpinning their aggressive proliferative behaviour remain incompletely characterised, and median overall survival for patients with glioblastoma—the most malignant grade—remains dismal even under optimally delivered multimodal therapy. Epigenetic dysregulation has emerged as a central theme in glioma pathogenesis, with Polycomb group proteins occupying a particularly prominent position in this landscape. Chromobox protein homologue 2 (CBX2) is a chromodomain-containing component of Polycomb Repressive Complex 1 (PRC1) that mediates transcriptional silencing through recognition of the repressive histone mark H3K27me3 and facilitation of histone H2A monoubiquitination at lysine 119. Accumulating evidence from pan-cancer transcriptomic analyses and molecular cell biology indicates that CBX2 is aberrantly overexpressed in multiple solid malignancies and that its oncogenic activity encompasses the repression of senescence-associated tumour suppressors, dysregulation of cell cycle progression, and maintenance of stem-like cellular states. Within the glioma context, CBX2 overexpression intersects with established epigenetic drivers—including IDH mutation-associated methylation phenotypes and H3K27M oncohistone mechanisms—to sustain unchecked proliferation and confer resistance to standard therapeutic interventions. This article provides a comprehensive narrative review of the molecular architecture and canonical biology of CBX2, synthesises current evidence concerning its dysregulation and functional consequences in gliomas, examines its interactions with downstream proliferative signalling networks, and considers its emerging potential as a therapeutic target. Whilst the direct experimental evidence specifically linking CBX2 to glioma proliferation remains in relatively early development compared to its better-characterised roles in other cancers, convergent data from epigenomic, transcriptomic, and functional studies make a compelling case for deeper investigation of this Polycomb subunit in neuro-oncological research.