We demonstrate that therapeutical intervention on the transcriptional pathways mediated by AP‐1, SMAD3 and RUNX1/RUNX2, combined with the GBM standard‐of‐care treatment based on temozolomide, led to the pronounced impairment of tumour growth, which was more evident in the context of the MS‐like subtype. Here, RUNX2 is linked to neoplasm.