In contrast, the constitutively-active Smad3 significantly rescues GBM cells from irinotecan single-agent cytotoxicity (and partially rescues from combination treatment toxicity), suggesting that irinotecan toxicity is partially mediated by TGF-β inhibition and that adding simvastatin alters how TGF-β is inhibited. Here, SMAD3 is linked to glioblastoma.