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纳米改性策略克服非小细胞肺癌中表皮生长因子受体酪氨酸激酶抑制剂耐药性。

Nanomodified strategies to overcome EGFR-tyrosine kinase inhibitors resistance in non-small cell lung cancer.

机构信息

Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung 80424, Taiwan.

Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.

出版信息

J Control Release. 2020 Aug 10;324:482-492. doi: 10.1016/j.jconrel.2020.05.043. Epub 2020 Jun 1.

Abstract

Lung cancer is the primary cause of cancer-related death worldwide. 85%-90% of cases are non-small cell lung cancer (NSCLC) which characteristically exhibits altered epidermal growth factor receptor (EGFR) signaling is a major driver pathway. Unfortunately, therapeutic outcomes in treating NSCLC are compromised by the emergence of drug resistance in response to EGFR-tyrosine kinase inhibitor (TKI) targeted therapy due to the acquired resistance mutation EGFR T790M or activation of alternative pathways. There is current need for a new generation of TKIs to be developed to treat EGFR-TKI-resistant NSCLC. To overcome the above problems and improve clinical efficacy, nanotechnology with targeting abilities and sustained release has been proposed for EGFR-TKI-resistant NSCLC treatment and has already achieved success in in vitro or in vivo models. In this review, we summarize and illustrate representative nano-formulations targeting EGFR-TKI-resistant NSCLC. The described advances may pave the way to better understanding and design of nanocarriers and multifunctional nanosystems for efficient treatment for drug resistant NSCLC.

摘要

肺癌是全球癌症相关死亡的主要原因。85%-90%的病例是非小细胞肺癌(NSCLC),其特征是表皮生长因子受体(EGFR)信号改变,是主要的驱动途径。不幸的是,由于获得性耐药突变 EGFR T790M 或其他途径的激活,针对 EGFR-酪氨酸激酶抑制剂(TKI)的靶向治疗药物的出现,导致对 NSCLC 的治疗出现耐药,从而影响了治疗效果。目前需要开发新一代 TKI 来治疗 EGFR-TKI 耐药的 NSCLC。为了克服上述问题并提高临床疗效,具有靶向能力和持续释放的纳米技术已被提议用于治疗 EGFR-TKI 耐药的 NSCLC,并已在体外或体内模型中取得成功。在这篇综述中,我们总结并说明了针对 EGFR-TKI 耐药 NSCLC 的代表性纳米制剂。所描述的进展可能为更好地理解和设计用于有效治疗耐药 NSCLC 的纳米载体和多功能纳米系统铺平道路。

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