Hepatocellular carcinoma (HCC) is associated with increased incidence worldwide. The treatment modalities remain limited. Surgery, radiofrequency, TACE and liver transplantation may be good therapeutic options for HCC patients; however, limited numbers of these patients are eligible for those therapeutic methods. In addition, HCC is resistant to systemic chemotherapy. Molecular targeted therapy shows promise results in HCC treatment. Recent studies are directed to identification of different molecular targets and related signaling pathways that converge in regulation of HCC growth and differentiation. The use of HCC animal models, HCC cell line as well as analysis of human HCC tissue samples, has pointed out the secrets of the molecular interactions that yield the development of HCC.
Growth factors such as HGF, EGF, VEGF, IGF, and TGF-ɑ are considered as invivo regulator of HCC. Growth factors associated signaling pathways are important targets for designing various pharmacological interventions. The impact of upregulation of signaling pathways such as PI3K –AKT/PKB, WNT/β-CATENIN in modifying the progress of HCC growth are promising pathways . Strategy target surface proteins in the Wnt pathway may be an attractive approach in HCC.
Spontaneous regression of HCC in some cases refers to the potential role of immunotherapy of HCC. Different immuno checkpoints have been identified. Immunotherapeutic agents such as Tremelimumab, a fully human IgG2 monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), has shown preliminary evidence of safety and efficacy in advanced HCC. Different T cell associated immunotherapeutic agents are in phase I or II clinical studies.
Pharmacogenomics studies that help in selecting patients who may benefit from specific chemotherapy that best matches his genomic profile are promising researches that increase efficacy and decreasing toxicity of drugs. Researches in these new interventions of HCC are welcomed to be part of this special issue.