预测索拉非尼治疗晚期肝细胞肝癌疗效的生物标志物研究进展

Advances in biomarkers predicting the efficacy of sorafenib in advanced hepatocellular carcinoma

肝细胞肝癌(hepatocellular carcinoma,HCC)是人类常见的恶性肿瘤,在所有恶性肿瘤中其死亡率位居第3位。目前,索拉非尼是晚期HCC唯一批准上市的分子靶向治疗药物。然而,索拉非尼在晚期HCC中的治疗效果并不理想,存在较大的个体差异。为了优化晚期HCC患者的治疗方案,减少医疗支出,改善患者的生活质量,人们对预测索拉非尼治疗晚期HCC疗效生物标志物的研究越来越重视。研究表明,肿瘤组织中磷酸化细胞外调节蛋白激酶(phosphorylated extracellular signal regulated kinase,p ERK)、c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)信号通路下游的c-Jun磷酸化水平和血管内皮生长因子受体2(vascular endothelial growth factor receptor-2,VEGFR-2)的表达水平,血清中甲胎蛋白(alpha-fetoprotein,AFP)、转化生长因子(transforming growth factor,TGF)和血管内皮生长因子(vascular endothelial growth factor,VEGF)的浓度,以及循环肿瘤细胞中p ERK和磷酸化蛋白激酶B(protein kinase B,PKB,又称Akt)的表达,是预测索拉非尼疗效的重要因素,具有作为新的生物标志物的应用前景。本文对近年来的相关临床队列研究进行综述。

Hepatocellular carcinoma （HCC） is a common kind of cancer in human beings, and ranks the third in cancer-related death. Nowadays, sorafenib is the only approved molecular targeted agent for the treatment of advanced HCC. However, the efficacy of sorafenib varies among individuals, which is unsatisfactory. People have researched some biomarkers predicting the efficacy of sorafenib in order to optimize treatment scheme, reduce health care expenses and improve the quality of life for advanced HCC patients treated with sorafenib. The studies show that the expressions of phosphorylated extracellular signal regulated kinase （pERK）, phosphorylated c-Jun at the downstream of c-Jun N-terminal kinase （JNK） signal pathway,vascular endothelial growth factor receptor-2 （VEGFR-2） in tumor tissues, alpha-fetoprotein （AFP）, transforming growth factor （TGF） and vascular endothelial growth factor （VEGF） in peripheral blood, as well as pERK/phosphorylated Akt （pAkt） expression in circulating tumor cells, are important factors to predict the efficacy of sorafenib, so these molecules have the potential of acting as predictive biomarkers for sorafenib treatment. This paper summarizes the recent clinical cohort studies on this topic.