Recent Progress on Sorafenib Resistance in Hepatocellular Carcinoma Mediated by Tumor Microenvironment
Hepatocellular carcinoma(HCC)was one of the most common malignant tumors in the world,accounting for about 90％of primary liver cancers,and the incidence of HCC were increasing year by year.Sorafenib,a multi-targeted tyrosine kinase inhibitor,had played an anti-HCC role by inhibiting tumor cell proliferation,tumor neovascularization,and tumor microenvironment remode-ling.Sorafenib had been approved as a first-line systematic therapy for advanced HCC patients,significantly prolonging the overall survival of some HCC patients.However,a large number of HCC patients still exhibited primary and acquired resistance to sorafenib,resulting in a worse prognosis for this patient population.Therefore,it was urgent to elucidate the mechanism of tumor microenviron-ment mediating the development of sorafenib resistance in HCC patients and develop intervention strategies.Studies have shown that the tumor microenvironment of HCC patients was closely related to the development of sorafenib resistance.The tumor microenviron-ment consisted of various cellular and non-cellular components,such as tumor-associated macrophages,cancer-associated fibroblasts,tumor-associated neutrophils,extracellular matrix,cytokines,and chemokines.These components interacted with each other and with tumor cells,forming a complex network that modulated the biological behavior and drug response of HCC.The mechanism of sorafenib resistance mediated by tumor microenvironment in hepatocellular carcinoma was reviewed in this article,mainly focusing on hypoxia,tumor-associated immune-suppressive cells and cancer-associated fibroblasts.Based on the current understanding of the mechanism of sorafenib resistance mediated by tumor microenvironment in hepatocellular carcinoma,this article also discussed the potential strate-gies to overcome sorafenib resistance,such as targeting the key molecules or pathways involved in the tumor microenvironment,and using biomarkers to predict the sorafenib response and select the optimal treatment regimen.This article aimed to provide new ideas for the clinical treatment of hepatocellular carcinoma patients in the future and in order to prolong the overall survival of HCC patients.
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