“…Similarly, an incremental activation of mTOR was detected in HCC, dysplastic nodules and non-neoplastic surrounding tissues when compared with normal livers, with the highest expression being in HCC [57,58]. In HCCs, activation of the mTOR signaling has been associated with poor differentiation, high TNM and BCLC staging, high AFP, intra-hepatic metastasis, vascular invasion, angiogenesis, high proliferation index and post-transplant recurrence; whereas inhibition of mTOR could suppress tumor growth and sensitize tumor cell to chemotherapy or other targeted therapies [53,54,56,57,[59][60][61][62]. In several preclinical studies, liver-specific TSC1 knockout mice showed constitutively elevated mTOR signaling and developed sporadic HCC [38,55,63,64].…”