Molecular Mechanisms and Therapeutic Targets of Hepatitis B Virus Pre-S Mutant-Associated Hepatocellular Carcinoma Tumorigenesis

Background: Despite significant progress in diagnosis and therapeutics, hepatocellular carcinoma (HCC) is still among the most commonly occurring and life-taking human cancers globally, raising an urgent need for discovering effective therapeutic targets. Purpose: Chronic hepatitis B virus (HBV) infection is a major etiological factor associated with HCC development, progression, and prognosis. Pre-S mutants are naturally occurring mutated forms of HBV large surface proteins and predict a higher risk of HCC development and recurrence. Moreover, pre-S mutants function as important HBV oncoproteins which can promote HCC tumorigenesis through initiating a variety of oncogenic signaling pathways. Targeting pre-S mutant-induced oncogenic signaling pathways displays therapeutic potential in HCC. Research Design: This review summarizes the underlying molecular mechanisms of pre-S mutant-associated HCC tumorigenesis and highlights their potential in serving as therapeutic targets for HCC.