原发性肝细胞癌对索拉非尼耐药机制的研究进展

索拉非尼是目前公认的治疗晚期原发性肝细胞癌的分子靶向药物,但原发性肝细胞癌对其耐药性的出现,影响了药物对肝癌的疗效。原发性肝细胞癌对索拉非尼耐药存在多种机制。肝癌细胞本身表皮生长因子受体的表达上调及其下游信号通路的异常改变,沉默信息调节因子1的过表达,肝癌细胞的自噬能力增强及间充质转变均可能导致其对索拉非尼耐药。肝癌血管内皮细胞出现耐药,肿瘤微环境中缺氧诱导因子-1α、趋化因子及其受体上调等也可能影响肿瘤对索拉非尼的敏感性。该文就原发性肝细胞癌对索拉非尼耐药机制的研究进展进行综述。

Mechanisms of drug resistance to sorafenib in hepatocellular carcinoma

Sorafenib is the currently accepted first-line drug used for the treatment of advanced hepatocellular carcinoma,while resistance to sorafenib affects its curative effect.Available studies elucidated multiple mechanisms responsible for the resistance to sorafenib.The up-regulation of EGFR,dysregulation of signal pathways downstream of EGFR,and overexpression of silent information regulator 1 in hepatoma cells as well as epithelial-to-mesenchymal transition and increased autophage ability of hepatoma cells may increase the resistance to sorafenib.Resistance in tumor endothelial cells and the upregulation of hypoxia-induced factor-1α,chemokine and its receptors in the tumor microenvironment may also affect the sensitivity of hepatcellular carcinoma to sorafenib.This review provides an overview of the underlying mechanisms related to resistance to sorafenib of hepatocellular carcinoma.