Some New Approaches to the Management of Hepatocellular Carcinoma

A concordance of multiple advances is changing the management of hepatocellular carcinoma (HCC). These include: (1) identification of preventable and treatable causal factors, including hepatitis B and obesity (non-alcoholic steatotic hepatitis [NASH]); (2) description of molecular and proteomic profiles for HCC prognosis, disease subtyping, and drug selection; (3) identification of circulating tumor cells for non-invasive molecular typing; (4) identification of tumor stem cells, for HCC subtyping and as treatment targets; (5) large numbers of multi-kinase inhibitors that are currently undergoing clinical trial assessment and comparison; (6) an array of newer therapies of different drug classes, aimed at a wide range of targets in cell growth, apoptosis, autophagy, and tumor invasion pathways; (7) newer regional chemotherapy and radiotherapy regimens and delivery systems; (8) the extension of liver transplantation to larger HCCs and its wider availability through use of living-related organ donors; (9) new radiological techniques to assess the changes in HCC vascularity associated with angiogenic drug actions; (10) re-evaluation of the importance of tumor biopsy to obtain molecular signatures; (11) recognition of the importance of non-tumor liver parenchyma for tumor growth control and as a source of prognostic profiling in HCC patients; (12) the evaluation of kinase- and other inhibitors in neo-adjuvant and adjuvant therapy associated with resection and liver transplant and minimization of transplant waiting list drop-out; (13) re-evaluation of the role or limitation of tumor responses, since kinase inhibitors can enhance survival without HCC size responses; and (14) the development of combination therapies to enhance tumor control rates, either using drugs targeting differing pathways, or kinase-inhibitors combined with either chemotherapy drugs or yttrium 90.