DUSP6/MKP3 as an emerging therapeutic target in glioblastoma.

The role of MKP family dual-specificity phosphatases (DUSPs) in oncogenesis, together with their potential as therapeutic targets in precision oncology, is now well established. These enzymes dephosphorylate both phosphotyrosine and phosphothreonine residues on extracellular signal-regulated kinase ERK1/2, thereby attenuating mitogen-activated protein kinase (MAPK) signalling. DUSP6/MKP3 acts as a context-dependent regulator with tumour-suppressive or tumour-promoting roles across cancers. Glioblastoma (GBM), an aggressive primary brain tumour with dismal clinical outcomes, has shown limited response to both oncogene-targeted and immunotherapeutic approaches. DUSP6/MKP3 is frequently overexpressed in GBM and contributes to tumour growth, invasive behaviour, and treatment resistance. Computational analyses identify DUSP family genes, including DUSP6/MKP3, as recurrently dysregulated within GBM driver networks, supporting a central role in gliomagenesis. Here, we discuss DUSP6/MKP3 in glioblastoma, integrating transcriptional and cell-based evidence to define its molecular mechanisms and clinical relevance.