Anticancer activity of combination targeted therapy using cetuximab plus vemurafenib for refractory BRAFV600E-mutant metastatic colorectal carcinoma
Anticancer activity of combination targeted therapy using cetuximab plus vemurafenib for refractory BRAFV600E-mutant metastatic colorectal carcinoma
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DOI：
10.3747/co.21.1661
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发表时间：
2014-02-01
期刊：
影响因子：
2.6
通讯作者：
Epstein, R. J.
中科院分区：
文献类型：
--
作者：
Connolly, K.;Brungs, D.;Epstein, R. J.
错配修复缺陷型结直肠癌通常含有激酶激活V600E BRAF突变，但在这种情况下，使用口服BRAF激酶抑制剂（如维罗非尼或达拉非尼）进行单药治疗尚未证明临床效用。最近的研究表明，肿瘤对BRAF抑制的耐药性是由上调的表皮生长因子受体（EGFR）信号传导介导的，其破坏是KRAS野生型结直肠癌的常规治疗策略。在这份报告中，我们描述了一个严重的预治疗患者的临床过程中，谁选择接受标签外的双重靶向BRAF和EGFR抑制治疗，具有良好的耐受性和明显的临床效益。
Mismatch-repair-deficient colorectal cancers often contain kinase-activating V600E BRAF mutations, but no clinical utility has yet been demonstrated in this setting for monotherapy using oral BRAF kinase inhibitors such as vemurafenib or dabrafenib. Recent studies have indicated that tumour resistance to BRAF inhibition is mediated by upregulated epidermal growth factor receptor (EGFR) signalling, disruption of which is a routine treatment strategy in KRAS wildtype colorectal cancer. In this report, we describe the clinical course of a heavily pretreated patient who elected to receive off-label dual-targeted BRAF- and EGFR-inhibitory therapy with good tolerance and apparent clinical benefit.