PRDM players in Central Nervous System Cancers: state of the art and future perspectives

Despite major advances in understanding the molecular landscape of brain cancer, diagnosis is challenging and current treatment options remain largely ineffective. This underscores the urgent need to identify further genes and molecular pathways that could serve as therapeutic targets. PR (PRDI-BF1 and RIZ) domain-containing (PRDM) proteins, long recognized as key regulators in several cancer types, represent an emerging, yet still poorly understood, determinant of brain cancers. In this manuscript, we review current knowledge on the involvement of PRDM proteins (PRDMs) in central nervous system malignancies, suggesting their potential as diagnostic and prognostic biomarkers. We further discuss therapeutic perspectives, including strategies aimed at modulating PRDMs expression, targeting PRDMs-driven pathways, or affecting their enzymatic activities. Together, these insights position PRDMs as promising candidates for next-generation mechanism-based interventions that could optimize brain cancer treatment. • PRDMs are emerging biomarkers able to improve diagnosis and prognosis in CNS tumors • Altered PRDM isoforms drive therapy resistance and reveal new treatment targets • PRDMs control metabolic, vascular and immune features affecting treatment outcomes • Modulating PRDM activity may help overcome GBM heterogeneity and therapy resistance • PRDM profiling could refine precision medicine for patients with brain cancers