Although Smad3 functions are modulated through phosphorylation of the linker region by intracellular kinases [69], and previous studies in HCC tumor models indicate that Smad3 linker phosphorylation attenuates TGF‐β transcriptional activities, thereby facilitating the transition between TGF‐β‐mediated growth suppression and oncogenic signaling [70], it appears that this mechanism contributes minimally to the resistance phenomenon. The gene discussed is SMAD3; the disease is neoplasm.