SMAD2 and neoplasm: As mentioned above, TGFβ signaling plays important roles in driving oncogenesis and blocking this pathway has shown promising anti-tumor activity.1,2 In GBM, previous approaches to block TGFβ signaling have encompassed a TGFBR1 small molecule inhibitor (galunisertib) and an ASO against TGFβ2 (trabedersen), both of which did not show improvements in overall survival in phase II trials.43,44 These efforts have mainly focused on targeting the TGFβ:TGFBR1 axis without much focus on either TGFBR2 or the complexity of downstream SMAD2/3 signaling and gene regulation.