Therapeutic targeting of TβRI/II or TβRIII significantly attenuates the formation and progression of precancerous lesions and demonstrates potent tumor growth suppression in vivo.213–215 In oral premalignancy, cytoplasmic phosphorylated SMAD3 (p-SMAD3) creates a nonfunctional state.216 In addition, bone morphogenetic protein (BMP) pathway inhibition disrupts gastric lineage differentiation. This evidence concerns the gene SMAD3 and neoplasm.