Signaling Pathway Remodeling and Molecular Regulation in the HCC TME: Dynamic Evolution and Clinical Therapeutic Advances

The dynamic evolution of signaling pathway remodeling and molecular regulation within the tumor microenvironment (TME) of hepatocellular carcinoma (HCC) play a critical role in the onset and progression of this malignancy. As chronic hepatitis progresses to cirrhosis and ultimately to HCC, the signaling pathways and TME show stage-specific characteristics that provide important insights into the therapeutic challenges and opportunities. In this review, we profiled the principal components of the HCC TME, along with pivotal signaling pathways, including the receptor tyrosine kinase (RTK) and extracellular signal-regulated kinase (ERK) pathways. Furthermore, we characterized the dynamic transformation of the TME from an inflammatory state in the hepatitis phase to a fibrotic state in the cirrhosis phase. Ultimately, we assessed the therapeutic potential of current HCC targets emphasizing emerging strategies for precision and personalized treatment.