Notch signaling in hepatocellular carcinoma: molecular targeting in an advanced disease

The use of alternative therapeutic approaches in advanced carcinogenesis is a growing investigative base. One such cancer, primary liver cancer, is one of the most commonly occurring cancers worldwide and often presents in late stage disease consequently preventing traditional curative modalities. As a result, hepatocellular carcinoma (HCC), representing the majority of primary liver cancer, is the third most common cause of cancer-related deaths globally. Survival rates are linked to stage of presentation as well as concomitant cirrhosis limiting the 5-year survival in these patients to < 20%. Alternative strategies are in dire need as patients in this cohort have limited palliative options. Currently, sorafenib is the only approved systemic therapy; however, it has a limited survival advantage and low efficacy prompting the empirical need for further evaluation. Understanding of cancer therapy has led to an enhanced focus on the Notch pathway as a potential target for advanced HCC. Notch signaling is a critical component of development and cell fate and has been linked to various modalities including liver regeneration and as a key driver in carcinogenesis. In this review, we will provide a review of the current status of the Notch signaling in liver cancer and of Notch as an alternative potential strategy for advanced HCC