Hepatology：索拉非尼治疗肝癌个体差异原因

2015-10-18 MedSci MedSci原创

中科院上海生科院营养科学研究所谢东研究组在最新研究中发现了索拉菲尼治疗肝癌疗效的个体差异原因及机制。相关成果日前在线发表于《肝脏学》期刊。索拉菲尼作为一类有效的ATP竞争型RAF激酶抑制剂，是近年来第一个用于治疗晚期肝癌的分子靶向型药物，能有效抑制肿瘤细胞生长和血管生成。但临床研究显示，索拉菲尼在肝癌治疗上的响应率较低，疗效有明显的个体差异，但其原发性和获得性耐药的原因及内在机制尚不清楚。在谢东的

中科院上海生科院营养科学研究所谢东研究组在最新研究中发现了索拉菲尼治疗肝癌疗效的个体差异原因及机制。相关成果日前在线发表于《肝脏学》期刊。

索拉菲尼作为一类有效的ATP竞争型RAF激酶抑制剂，是近年来第一个用于治疗晚期肝癌的分子靶向型药物，能有效抑制肿瘤细胞生长和血管生成。但临床研究显示，索拉菲尼在肝癌治疗上的响应率较低，疗效有明显的个体差异，但其原发性和获得性耐药的原因及内在机制尚不清楚。

在谢东的指导下，关东铣博士等利用临床肝癌病人来源和人肝癌细胞系来源的异种肝癌，原位移植荷瘤小鼠模型及肝原位细胞注射荷瘤模型，模拟和探索索拉菲尼在肝癌治疗中的耐药问题。研究发现，索拉菲尼对肝癌的疗效跟肝癌干细胞对其响应密切相关。在部分肝癌病人中，索拉菲尼不但没有抑制效果，反而通过富集肝癌干细胞，加剧了肝癌的恶化。进一步研究表明，抑癌基因TSC2在索拉菲尼刺激下变成“促癌因子”进而介导耐药信号的传递。

同时，针对该耐药性肝癌，研究人员利用全反式维甲酸作为分化诱导剂，联合索拉菲尼用药，探索了行之有效而且简单易行的治疗新策略。专家认为，研究为临床上索拉菲尼治疗肝癌的适宜人群及耐药性，提供了有力的实验依据。

原始出处：

Li X, Yao W, Yuan Y, Chen P, Li B, Li J, Chu R, Song H, Xie D, Jiang X, Wang H.Targeting of tumour-infiltrating macrophages via CCL2/CCR2 signalling as a therapeutic strategy against hepatocellular carcinoma. Gut. 2015 Oct 9. pii: gutjnl-2015-310514

Guan DX, Shi J, Zhang Y, Zhao JS, Long LY, Chen TW, Zhang EB, Feng YY, Bao WD, Deng YZ, Qiu L, Zhang XL, Koeffler HP, Li JJ, Cheng S, Xie D.Sorafenib enriches EpCAM positive tumor initiating cells and exacerbates a subtype of hepatocellular carcinoma through TSC2-AKT cascade.Hepatology. 2015 Aug 7. doi: 10.1002/hep.28117

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160 0
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2016-03-07 忠诚向上

好好学习，继续努力

129 0
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2016-03-07 忠诚向上

好好学习，继续努力

136 0
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2016-03-07 忠诚向上

好好学习，继续努力

174 0
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2016-03-07 忠诚向上

好好学习，继续努力

148 0
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2016-03-07 忠诚向上

好好学习，继续努力

88 0
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2016-03-07 忠诚向上

好好学习，继续努力

127 0
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2016-03-07 忠诚向上

好好学习，继续努力

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