In addition to cancer development, the PI3K/Akt/Nrf2 pathway also participates in the regulation of chemoresistance [49, 50], and our study verified that M2-CM macrophage secreted VEGF to increase TMZ resistance in the GBM cells, which are supported by the facts that VEGF enhanced chemoresistance for multiple chemical drugs [61]. The gene discussed is VEGFA; the disease is glioblastoma.