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Hepatocellular carcinoma (HCC) is a malignant tumor that arises from hepatocytes. Multiple signaling pathways play a regulatory role in the occurrence and development of HCC, with the Wnt signaling pathway being one of the primary regulatory pathways. In normal hepatocytes, the Wnt signaling pathway maintains cell regeneration and organ development. However, when aberrant activated, the Wnt pathway is closely associated with invasion, cancer stem cells(CSCs), drug resistance, and immune evasion in HCC. Among these factors, the development of drug resistance is one of the most important factors affecting the efficacy of HCC treatment. These mechanisms form the basis for tumor cell adaptation and evolution within the body, enabling continuous changes in tumor cells, resistance to drugs and immune system attacks, leading to metastasis and recurrence. In recent years, there have been numerous new discoveries regarding these mechanisms. An increasing number of drugs targeting the Wnt signaling pathway have been developed, with some already entering clinical trials. Therefore, this review encompasses the latest research on the role of the Wnt signaling pathway in the onset and progression of HCC, as well as advancements in its therapeutic strategies.

Among primary liver cancers, hepatocellular carcinoma is the most common pathological type. Its onset is insidious, and most patients have no obvious discomfort in the early stage, so it is found late, and the opportunity for surgical radical treatment is lost, resulting in a poor prognosis. With the introduction of molecular-targeted drugs represented by sorafenib, patients with middle- and late-stage liver cancer have regained the light of day. However, their therapeutic efficacy is relatively low due to the limited target of drug action, toxic side effects, and other reasons. At this time, the emergence of immunotherapy represented by immune checkpoint inhibitors (ICIs) well breaks this embarrassing situation, which mainly achieves the anti-tumor purpose by improving the tumor immune microenvironment. Currently, ICI monotherapy, as well as combination therapy, has been widely used in the clinic, further prolonging the survival of patients with advanced hepatocellular carcinoma. This article reviews the development of monotherapy and combination therapy for ICIs in advanced hepatocellular carcinoma and the latest research progress.