Evaluation of the Glypican-3 promoter for transcriptional targeting of Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and represents the third most common cause of death from cancer globally. Limited therapeutic options, especially in an advanced stage, combined with the presence of underlying liver dysfunction in most of the patients limit its treatment. Targeted gene therapy may be a promising treatment in this setting. Transcriptional targeting of cancer can be achieved using promoters preferentially active in tumor cells (tumor specific promoters (TSPs)). Glypican 3 (GPC3) is an oncofetal protein belonging to the proteoglycan family and is highly expressed in HCC and not in normal or cirrhotic liver. Given the HCC-specific nature of GPC3 expression, we hypothesized that the promoter for this gene should be preferentially active in HCC.