Targeting Cell Death and Survival Receptors in Hepatocellular Carcinoma

Jordi      Muntane

Abstract

Hepatocarcinoma (HCC) is the fifth most common neoplasia in the world, and the first cause of death by cancer in some areas. The clinical course of HCC patients has improved greatly owing to the use of the oral multikinase inhibitor, Sorafenib. The expression of receptors belonging to the superfamily of tumor necrosis factor receptors (TNF-R), such as TNF-R1, CD95 and TNF-related apoptosis inducing ligand (TRAIL) receptor -1 (TRAIL-R1) and -2 (TRAIL-R2) are altered in patients with HCC, especially those in advanced stages of de-differentiation. The disruption of death receptor (DR)-dependent cell signaling is related to poor survival in patients with HCC. These observations, together with the lack of antitumoral therapy alternatives, have stimulated research on DR-targeted therapies. The increasing research progress in cell death shows the intense crosstalk among DR and cell survival pathways in cancer cells. In consequence, new potential therapeutic strategies involving antibodies or small molecules specifically targeted to DR pathways either in monotherapy or in combination with other therapeutic strategies may be envisaged in the future to treat HCC.

Keywords: Apoptosis, Cancer, Cell death receptors, TNF, CD95, Trail, TARGETING TNF-R TYPE I, NECROSIS FACTOR, HCC, TNF-R1 expression, malignant HCC phenotype, CD95 agonistic antibodies, radiotherapy, DISC complex