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目的胰岛素样生长因子/胰岛素系统参与乳腺癌肿瘤细胞的增殖、分化、浸润和转移过程,这为乳腺癌靶向治疗提供了一个新方向。本研究旨在总结国内外该系统抑制剂在乳腺癌靶向治疗方面的研究进展。方法利用PubMed、SciencceDirect和万方数据知识服务平台等数据库,以“胰岛素样生长因子/胰岛素系统、乳腺癌和靶向治疗”等为关键词,检索1995-10-2015-10的相关文献,其中英文文献1 431条,中文文献46条。纳入标准:(1)关于胰岛素样生长因子/胰岛素系统抑制剂和乳腺癌靶向治疗的临床和基础研究;(2)胰岛素样生长因子/胰岛素系统与乳腺癌患病风险的流行病学调查;(3)胰岛素样生长因子/胰岛素系统的构成及信号通路的相关研究。剔除标准:(1)存在研究设计缺陷或统计方法错误,质量差;(2)数据不完整,结局效应不明确。根据上述标准纳入67篇文献进行分析。结果外周血的高胰岛素样生长因子水平、高配体结合蛋白水平与乳腺癌的患病风险相关,而乳腺癌组织中的胰岛素样生长因子受体也呈现高表达趋势。大量实验表明,作用于胰岛素样生长因子/胰岛素系统的配体、配体结合蛋白、受体及下游信号通路等的抑制剂,以及与其他相关系统的联合抑制剂,具有抗肿瘤作用,且部分抑制剂已进入临床Ⅰ~Ⅲ期研究,并取得有效成果。然而也出现了一些失败的例子,这可能与该系统的复杂性和多变性相关。结论以胰岛素样生长因子/胰岛素系统为靶点的药物研究是乳腺癌治疗领域的新热点,但对该系统的作用机制和如何更好地应用于临床的研究还有待进一步完善和深入。
Objective The insulin-like growth factor/insulin system is involved in the proliferation, differentiation, infiltration and metastasis of breast cancer cells, which provides a new direction for breast cancer targeted therapy. This study aims to summarize the research progress of the systemic inhibitors in breast cancer targeted therapy at home and abroad. Methods Databases such as PubMed, SciencceDirect, and Wanfang Data Knowledge Service Platform were used to search for keywords such as “insulin-like growth factor/insulin system, breast cancer, and targeted therapy”, and searched for related literature on 1995-10-2015-10. Among them, there are 1 431 English documents and 46 Chinese documents. Inclusion criteria: (1) Clinical and basic research on insulin-like growth factor/insulin system inhibitors and breast cancer targeted therapy; (2) Epidemiological investigation of insulin-like growth factor/insulin system and breast cancer risk; (3) The study of the composition and signal pathway of insulin-like growth factor/insulin system. Exclusion criteria: (1) There are research design defects or statistical method errors, and the quality is poor; (2) The data is incomplete and the outcome is not clear. Based on the above criteria, 67 articles were included for analysis. Results High levels of insulin-like growth factor and high ligand binding protein in peripheral blood were associated with the risk of breast cancer, and insulin-like growth factor receptors in breast cancer tissues also showed a high expression trend. Extensive experiments have shown that inhibitors of ligands, ligand binding proteins, receptors, and downstream signaling pathways acting on the insulin-like growth factor/insulin system, as well as co-inhibitors with other related systems, have anti-tumor effects, and some Inhibitors have entered clinical phase I-III studies and achieved effective results. However, there have also been some failed examples, which may be related to the complexity and variability of the system. Conclusions The study of insulin-like growth factor/insulin system as a target is a new hotspot in the field of breast cancer treatment. However, the mechanism of action of this system and how to better apply it to clinical research remain to be further improved and in-depth.