Table 1.

Chemical compounds affecting the mTOR signaling pathway currently used or under investigation in chronic liver diseases and hepatocellular carcinoma (HCC).

Drug Name	Pharmacological Group	Primary Target(s)	Licensed for	Pros and Cons
Sorafenib	Multikinase inhibitor	VEGFR, PDFGR, c-Kit, c-RAF and B-RAF	Standard of care for advanced unresectable HCC	Reduced tolerability, limited efficacy. Highly toxic when combined with mTOR inhibitors.
Rapamycin (sirolimus) and everolimus	mTOR inhibitor	Intracellular receptor FKBP12. Inhibition of mTORC1 (and mTORC2 to a lesser extent)	Immunosuppression after liver transplantation in combination with calcineurin inhibitors	Inefficacious in monotherapy for advanced HCC. Potential effect as adjuvant therapy after liver transplantation to prevent tumor recurrence in selected patients.
mTOR kinase inhibitors	mTOR inhibitor (ATP-competitive)	mTOR kinase domain. Inhibit both mTORC1 and mTORC2	Under investigation for advanced HCC	Ongoing clinical trials in HCC. Safety and efficacy still to be determined.
UDCA (and derivatives)	Bile acid	mTOR signalling pathway	Cholestatic diseases	Anti-tumor effect in preclinical models of HCC. Very well tolerated. No proven benefit for HCC in humans.