转移性结直肠癌抗EGFR治疗耐药机制的研究进展

Research progress in the resistance mechanism of anti-EGFR therapy in metastatic colorectal cancer

表皮生长因子受体(epidermal growth factor receptor,EGFR)是转移性结直肠癌(metastatic colorectal cancer,mCRC)的主要治疗靶点之一,然而抗EGFR治疗的耐药一直是亟待解决的临床难题。肿瘤细胞本身EGFR相关信号通路异常激活,基因组不稳定性等遗传学或表观遗传学改变是引发耐药最常见的机制,近期也有研究发现肿瘤微环境中细胞丰度和细胞因子的变化等也是引发抗EGFR治疗耐药的重要机制。我们将从肿瘤细胞和肿瘤微环境两个方面,对mCRC抗EGFR治疗的耐药机制进行综述。

Epidermal growth factor receptor(EGFR)is one of the primary therapeutic targets for metastatic colorectal cancer(mCRC).However,primary or acquired resistance to anti-EGFR therapy has long been a crucial problem to be solved urgently.Abnormal activation of EGFR-related signaling pathways in tumor cells,genomic instability and genetic or epigenetic changes are the most common mechanism of resistance to anti-EGFR therapy.Meanwhile,recent evidences showed that alterations of cell abundance and cytokines in the tumor microenvironment are also closely related to anti-EGFR therapy resistance.In this review,we will summarize the research progress about the mechanism of resistance to anti-EGFR therapy in CRC from the aspects of both the tumor cell and tumor microenvironment.