Department of Molecular Pharmacology and Experimental Therapeutics, Center for Individualized Medicine Epigenomics Program, Mayo Clinic, Rochester, MN, 55905.
Hepatocellular carcinoma (HCC) is among the fastest growing causes of cancer related death in the United States due to a lack of early detection strategies, increased incidence driven in part by metabolic syndrome, and limited treatment options. Multikinase inhibitors (sorafenib/regorafenib) and immune checkpoint inhibitors (nivolumab) are the three FDA-approved drugs for HCC treatment, with only the latter having potential to dramatically improve outcome, emphasizing the unmet need for alternative therapeutic strategies. In this issue of HEPATOLOGY, Liu et al. explore the role of the DNA methyltransferase inhibitor (DNMTi), SGI-110, for the treatment of HCC in preclinical models (1). SGI-110 (guadecitibine) is a second-generation DNMTi in which 5-aza-2'-deoxycytidine (5-azadC or decitabine) is linked to deoxyguanosine, conferring additional stability and longer half-life due to protection from deamination.