细胞自噬与EGFR抑制剂在肿瘤治疗中的研究进展 |
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引用本文: | 庞歆桥(综述),曹邦伟(审校). 细胞自噬与EGFR抑制剂在肿瘤治疗中的研究进展[J]. 国际病理科学与临床杂志, 2016, 0(5): 681-689. DOI: 10.3978/j.issn.2095-6959.2016.05.029 |
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作者姓名: | 庞歆桥(综述) 曹邦伟(审校) |
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作者单位: | 首都医科大学附属北京友谊医院肿瘤科,北京,100050 |
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基金项目: | 国家自然科学基金(81272615;81301912)。hTis work was supported by National Natural Science Foundation of China (81272615 |
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摘 要: | 表皮生长因子受体(EGFR)抑制剂是近些年来肿瘤治疗的新策略。然而,先天性或者获得性耐药问题成为其疗效的一大障碍。自噬,是一种细胞自我消化的过程,并与耐药具有相关性。EGFR的激活能够通过多种信号通路调节自噬过程。EGFR抑制剂能够诱导自噬,然而EGFR诱导自噬的这种特殊作用是双向的。一方面,自噬能够增强EGFR抑制剂的细胞毒性作用,从而成为一种细胞的保护措施;另一方面,EGFR抑制剂治疗后产生的高自噬水平同样能够导致细胞自吞噬性死亡,从而逃脱凋亡,当EGFR抑制剂与一种自噬诱导剂联合应用时可能会产生更显著的治疗作用。因此,调节自噬水平将成为提高肿瘤患者EGFR抑制剂治疗效果的可行之举。
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关 键 词: | 表皮生长因子受体-酪氨酸激酶抑制剂(EGFR-TKI) 吉非替尼 厄洛替尼 西妥昔单抗 自噬 耐药 |
Research progress of EGFR inhibitors and autophagy in cancer treatment |
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Abstract: | Epidermal growth factor receptor (EGFR) inhibitor treatment is a strategy for cancer therapy. However, innate or acquired resistance is a major obstacle of the effcacy. Autophagy is a self-digesting process in cells, which is considered to be associated with anti-cancer drug resistance. The activation of EGFR can regulate autophagy through multiple signal pathways. EGFR inhibitors can induce autophagy, but the specific function of the induction of autophagy by EGFR inhibitors remains biphasic. On the one hand, autophagy induced by EGFR inhibitors acts as a cytoprotective response in cancer cells, and autophagy inhibitors can enhance the cytotoxic effects of EGFR inhibitors. On the other hand, a high level of autophagy atfer treatment of EGFR inhibitors can also result in autophagic cell death lacking features of apoptosis, and the combination of EGFR inhibitors with an autophagy inducer might be beneifcial. hTus, autophagy regulation represents a promising approach for improving the effcacy of EGFR inhibitors in the treatment of cancer patients. |
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Keywords: | EGFR-TKI geiftinib erlotinib cetuximab EGFR autophagy resistance |
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