School of Preclinical Medicine, Chengdu University, Chengdu 610106, China.
National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China.
Mol Pharm. 2023 Feb 6;20(2):829-852. doi: 10.1021/acs.molpharmaceut.2c00792. Epub 2023 Jan 1.
Epidermal growth factor receptor (EGFR) plays a key role in signal transduction pathways associated with cell proliferation, growth, and survival. Its overexpression and aberrant activation in malignancy correlate with poor prognosis and short survival. Targeting inhibition of EGFR by small-molecular tyrosine kinase inhibitors (TKIs) is emerging as an important treatment model besides of chemotherapy, greatly reshaping the landscape of cancer therapy. However, they are still challenged by the off-targeted toxicity, relatively limited cancer types, and drug resistance after long-term therapy. In this review, we summarize the recent progress of oral, pulmonary, and injectable drug delivery systems for enhanced and targeting TKI delivery to tumors and reduced side effects. Importantly, EGFR-TKI-based combination therapies not only greatly broaden the applicable cancer types of EGFR-TKI but also significantly improve the anticancer effect. The mechanisms of TKI resistance are summarized, and current strategies to overcome TKI resistance as well as the application of TKI in reversing chemotherapy resistance are discussed. Finally, we provide a perspective on the future research of EGFR-TKI-based cancer therapy.
表皮生长因子受体（EGFR）在与细胞增殖、生长和存活相关的信号转导途径中发挥关键作用。其在恶性肿瘤中的过度表达和异常激活与不良预后和生存期短相关。通过小分子酪氨酸激酶抑制剂（TKI）靶向抑制 EGFR 已成为除化疗以外的重要治疗模式，极大地改变了癌症治疗的格局。然而，它们仍然面临着脱靶毒性、相对有限的癌症类型以及长期治疗后产生的耐药性等挑战。在本文中，我们总结了口服、肺部和注射用药物递送系统在增强和靶向 TKI 递送至肿瘤以及减少副作用方面的最新进展。重要的是，基于 EGFR-TKI 的联合治疗不仅大大拓宽了 EGFR-TKI 的适用癌症类型，而且还显著提高了抗癌效果。我们总结了 TKI 耐药的机制，并讨论了克服 TKI 耐药的当前策略以及 TKI 在逆转化疗耐药中的应用。最后，我们对基于 EGFR-TKI 的癌症治疗的未来研究提供了一个视角。
