SignalingPathways DrivingHepatocellularCarcinoma: CurrentResearchProgress

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Hepatocellular carcinoma (HCC) accounts for over 90% of primary liver malignancies, ranking as the third leading cause of tumor-related death worldwide. Chronic viral hepatitis, alcoholic liver injury, non-alcoholic steatohepatitis and aflatoxin exposure are core etiological factors, all triggering malignant transformation through persistent activation of oncogenic signal cascades. Abnormally regulated signaling pathways govern hepatocyte proliferation, apoptosis escape, epithelial-mesenchymal transition, angiogenesis and immune evasion, forming a complex regulatory network for hepatocarcinogenesis. This review systematically summarizes six core dysregulated pathways in HCC, including RTK/RAS/MAPK, PI3K/AKT/mTOR, Wnt/β-catenin, JAK/STAT3, Hippo and Hedgehog pathways. We elaborate their mutationpatterns,upstreaminducingfactors(HBx,metabolicstress,liver fibrosis)anddownstreamcarcinogeniceffects,analyzepathwaycrosstalk, and discuss translational value for targeted therapy and early diagnosis. Current limitationsofpathwayresearchandfuture researchdirectionsare also proposed to provide molecular theoretical basis for HCC precision preventionandtreatment.

• 1N44551X1B0B-2873.pdf