12年新文献_HCC对多吉美耐药的主要因素可能是EGFR的激活

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1. EGFR的激活促进了HCC细胞对多吉美的耐药。
2. 多吉美与EGFR抑制剂(易瑞沙、特罗凯、爱必妥等)的组合，有助于控制HCC增殖。

下不到全文。摘要中看，做的应该是in vitro的体外实验。

onlinelibrary.wiley.com/doi/10.1002/ijc.27604/abstract?deniedAccessCustomisedMessage=&userIsAuthenticated=false

EGFR activation is a potential determinant of primary resistance of hepatocellular carcinoma cells to sorafenib

Zakaria Ezzoukhry1,2, Christophe Louandre1,2, Eric Trécherel1,2, Corinne Godin1,2, Bruno Chauffert3, Sébastien Dupont1, Momar Diouf4, Jean-Claude Barbare4, Jean-Claude Mazière1,2, Antoine Galmiche1,2,†,*Article first published online: 30 APR 2012

International Journal of Cancer

Keywords:hepatocellular carcinoma;sorafenib;resistance;EGFR;RAF kinases
Abstract
Sorafenib is currently the medical treatment of reference for hepatocellular carcinoma (HCC), but it is not known whether sorafenib is equally active in all HCC. Here, our aim was to explore intrinsic differences in the response of HCC cells to sorafenib, to identify potential mechanisms leading to primary resistance to this treatment. We analyzed a panel of six human HCC cell lines and compared the activity of the main oncogenic kinase cascades, their clonogenic potential, proliferation and apoptosis upon exposure to sorafenib. We report that HCC cells present important differences in their response to sorafenib, and that some cell lines are more resistant to the actions of sorafenib than others. We identify the activated epidermal growth factor receptor (EGFR) as a parameter that promotes the resistance of HCC cells to sorafenib. In resistant cells, the efficacy of sorafenib was increased when EGFR was inhibited, as was demonstrated using two chemical inhibitors (erlotinib or gefitinib), a monoclonal antibody directed against EGFR (cetuximab), and RNA interference directed against EGFR. A combination of EGFR inhibitors and sorafenib affords a better control over HCC proliferation, most likely through an improved blockade of the RAF kinases. Our findings therefore confirm the importance of RAF kinases as therapeutic targets in HCC, and identify EGFR as a determinant of the sensitivity of HCC cells to sorafenib. Our findings bear possible implications for the improvement of the efficacy of sorafenib in HCC, and might be useful for the identification of predictive biomarkers in this context.

重生 · 发表于 2012-9-2 20:39:54

是不是说明多吉美耐药了，就可以吃易瑞沙、特罗凯、爱必妥等，正好我爸是肝转肺。我想是不是有效呢！

zhuynsky · 发表于 2012-9-12 22:33:02

多吉美可以和EGFR抑制剂(易瑞沙、特罗凯、爱必妥等)混着吃。。是怎么吃呢？
是吃一段时候多吉美换药呢，还是几种药同时吃？

flame13 · 发表于 2012-9-12 23:52:39

本帖最后由 flame13 于 2012-9-12 23:55 编辑

这说法太天真了，我论坛收集的数据，起码有接近10个人多吉美耐药后，用特罗凯或带EGFR靶点的药，全部无效，新人还是多看看贴，文献这种信一半好了，论坛的人是用生命作为代价试药的，与其相信看不到实例的文献，还不如多看一下正在用药的帖子，注意他们的指标变化，这种是文献提供不了的数据
越后来的人越有福气，请多点开动下脑筋{:soso_e113:}