Samah Saleh Ahmed Al-Awadhi

, Prakash Patil, Vijith V Shetty
* 
, Praveenkumar Shetty, Padma k Shetty, Reshma A Shetty
Abstract
Hepatocellular carcinoma (HCC) is the most prevalent type of primary liver cancer, accounting for roughly 90% of all liver malignancies worldwide, and remains the leading cause of cancer death worldwide. Cirrhosis, viral hepatitis, non-alcoholic fatty liver disease (NAFLD), or liver injuries caused by alcohol are all chronic diseases that have a close association with the pathogenesis of HCC. A key factor in the progression of these diseases to HCC is the activation of the epidermal growth factor receptor (EGFR) signaling pathway. The ErbB family of receptor tyrosine kinases, which includes EGFR, is essential for inflammation, cell division, and liver regeneration. In HCC, EGFR expression and hyperactivation are closely associated with tumor growth, metastasis, and patient prognosis. This review explores the structural and functional aspects of EGFR, its signaling mechanisms in hepatocellular proliferation and apoptosis, its role in liver fibrosis, and the transition from chronic liver injury to advanced HCC. Moreover, crosstalk between EGFR-mediated pathways and other signaling pathways, such as PI3K/AKT/mTOR and MAPK/ERK, contributes to resistance to targeted therapies, suggesting that molecular regulation needs to be improved in strategies targeting EGFR and its downstream pathways.