Mechanisms of resistance to anti-EGFR therapy in colorectal cancer.
Mechanisms of resistance to anti-EGFR therapy in colorectal cancer.
复制标题
结直肠癌抗EGFR治疗耐药机制
DOI：
10.18632/oncotarget.14012
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发表时间：
2017-01-17
期刊：
影响因子：
--
通讯作者：
Yuan X
中科院分区：
文献类型：
--
作者：
Zhao B;Wang L;Qiu H;Zhang M;Sun L;Peng P;Yu Q;Yuan X
单独靶向表皮生长因子受体 (EGFR) 或联合化疗对 RAS 野生型转移性结直肠癌 (mCRC) 患者有效。然而，只有一小部分转移性结直肠癌患者对抗 EGFR 治疗敏感，即使是最好的病例最终也会对该治疗产生耐药性。很明显，RAS 突变与抗 EGFR 治疗的耐药性相关。然而，这些耐药机制仅占无反应患者的近 35% 至 50%，这表明可能存在其他机制。事实上，近年来已经报道了几种导致逃避抗 EGFR 治疗的新途径。在这篇综述中，我们概述了导致原发性和获得性抗 EGFR 治疗耐药的已知和新机制，并列出了克服或逆转这种耐药性的可能治疗策略。
Targeting the epidermal growth factor receptor (EGFR) either alone or in combination with chemotherapy is effective for patients with RAS wild type metastatic colorectal cancer (mCRC). However, only a small percentage of mCRC patients are sensitive to anti-EGFR therapy and even the best cases finally become refractory to this therapy. It has become apparent that the RAS mutations correlate with resistance to anti-EGFR therapy. However, these resistance mechanisms only account for nearly 35% to 50% of nonresponsive patients, suggesting that there might be additional mechanisms. In fact, several novel pathways leading to escape from anti-EGFR therapy have been reported in recent years. In this review, we provide an overview of known and novel mechanisms that contribute to both primary and acquired anti-EGFR therapy resistance, and enlist possible treatment strategies to overcome or reverse this resistance.