Consistent with the prominent role of these TFs in GBM identified in our analyses, therapeutical targeting of the AP‐1 complex, RUNX1, RUNX2 or SMAD3 factors alone or in combination with the canonical GBM chemotherapeutic agent temozolomide displayed a subtype‐specific impairment on cell proliferation with greater effects in the context of the MS subtype. Here, RUNX2 is linked to myeloid sarcoma.