These results together suggest that EGFRvIII can regulate the expression of ALDH1A3 by activating the NF-κB pathway to promote proneural–mesenchymal transition of GBM and reduce its sensitivity to TMZ, which may be one of the important reasons why GBM patients with EGFRvIII (+) have low sensitivity to TMZ, potentially providing a new idea for clinical research and development of GBM treatment drugs. Here, NFKB1 is linked to glioblastoma.