Novel Oncogenes and Tumor Suppressor Genes in Hepatocellular Carcinoma: Carcinogenesis, Progression, and Therapeutic Targets Publisher Pubmed



Rahimifarsi N¹ ; Bostanian F² ; Shahbazi T³ ; Shamsinejad FS⁴ ; Bolideei M⁵ ; Mohseni P⁶ ; Zangooie A^{7, 8} ; Boustani F⁹ ; Shoorei H^{8, 9, 10} Show Affiliations
Source: Gene Published:2025

Abstract

Hepatocellular carcinoma (HCC) is the primary malignancy affecting the liver and the leading cause of mortality among individuals with cirrhosis. This complex disease is associated with various risk factors, including environmental, pathological, and genetic influences, which dysregulate gene expression crucial for the cell cycle and cellular/molecular pathways. The disruption of the balance between tumor suppressors and proto-oncogenes amplifies the pathogenic cascade. Given its predilection for diseased or cirrhotic livers and late-stage diagnosis, HCC prognosis is typically poor. Current therapies offer limited benefits, with conventional non-specific cytotoxic agents exhibiting suboptimal efficacy. However, molecularly targeted therapies have emerged as a promising avenue, leveraging the strategic inhibition of carcinogenic molecules to provide heightened specificity and potency compared to cytotoxic chemotherapy. Several clinical trials have demonstrated promising outcomes in advanced HCC with targeted pharmacotherapies. Many genes have been implicated in HCC pathogenesis, underscoring the need to elucidate their molecular functions and roles. This has profound implications for early HCC prognostication via biomarkers and for identifying therapeutic targets to impede neoplastic progression. Notably, evidence highlights the pivotal roles of oncogenes and tumor suppressors in HCC pathophysiology. This discourse examines the potential involvement of ABL1, Annexins, FAK, FOX, and KIF as candidate oncogenes, contrasted with SORBS2, HPCAL1, PCDH10, PLAC8, and CXXC5 as plausible tumor suppressors. Their signaling cascades and relevance to HCC prognosis and progression are delineated to identify targets for improving HCC diagnosis, prognostication, and therapy. © 2025 Elsevier B.V.