SMAD4 and cancer: Notably, C707 harbors a SMAD4 mutation (Table S1), further supporting a cancer cell extrinsic target that leads to tumor regression in response to TGF-βR1 inhibition.15, 33, 34 We next assessed drug response for CCIC line C1024, and find that within the VMT, C1024 is resistant to both FOLFOX and galunisertib until 6 days post-treatment, when both therapies result in about 50% regression in C1024 tumors (Fig 6, G).