Figure 2.

Concept of “clonal deletion and inhibition” therapy for hepatocellular carcinoma (HCC) chemoprevention and the effects of acyclic retinoid (ACR) on implementation of this concept. (a) Persistent inflammation caused by hepatitis viral infection transforms the liver into a precancerous field (“field cancerization”), which contains of multiple latent malignant clones that can, at some point, develop into HCC. (b) Even after early detection and removal of the primary HCC, the remaining clones survive in the remaining liver and grow into secondary HCC lesions (natural course), which is a major cause of the poor prognosis for patients with this malignancy. (c) Therefore, one of the most promising strategies to prevent secondary HCC is the deletion and inhibition of such transformed clones by inducing cell differentiation or apoptosis before the clones expand into clinically detectable tumors. This is the concept of “clonal deletion and inhibition” therapy for HCC chemoprevention. (d) ACR, which binds to RXRα and inhibits phosphorylation of this nuclear receptor, prevents the recurrence and development of secondary HCC via the mechanism described by this concept