肿瘤抗血管生成靶向药物耐药机制研究进展

Research progress of resistance to anti-angiogenic cancer treatments and its mechanism

目的:总结国内外关于肿瘤抗血管生成靶向药物耐药性机制的研究进展。方法:应用PubMed和CNKI期刊全文数据库检索系统,以"血管生成"和"耐药"和"肿瘤"为关键词,检索2001-01-2011-12相关文献共1 952篇,纳入标准:1)肿瘤抗血管生成耐药性分子机制;2)肿瘤抗血管生成耐药性调控;3)肿瘤抗血管生成耐药性预测指标。根据纳入标准,最后纳入分析30篇。结果:抗血管生成耐药性日益受到关注,可能的耐药机制包括血管生成多信号传导通路的影响、与血管内皮细胞相关的耐药机制、血管拟态、血管嵌入性生长等。直接与间接血管生成抑制剂联用可增加疗效,治疗过程中血压变化、循环血管生成因子有望成为预测抗血管生成药物疗效的指标。结论:单纯应用血管生成抑制剂很难取得持久疗效,容易出现耐药,但其机制目前还存在着争议,有待进一步研究明确。

OBJECTIVE：To summarize the progress of resistance to anti-angiogenic cancer treatments and its mecha- nism. METHODS： Totally 1 952 papers were searched with ＂angiogenesis＂ and ＂resistance＂ as key words within PubMed and CNKI database from January 2001 to December 2011 ,and 30 were finally screened out according to the inclusion crite ria as follows： 1） Molecular mechanism of anti-angiogenic resistance; 2）Regulations of anti-angiogenic resistance 3）Molec ular markers of anti-angiogenic resistance. RESULTS： Anti-angiogenic resistance has received more and more attention. The mechanisms may include several factors such as the influence of multiple signal transduction pathways in angiogene sis,factors related with vascular endothelial cell, vasculogenic mimicry and the embedding vessel growth. The curative effects could be enhanced by using directive and in-directive angiogenesis inhibitors simultaneously. Fluctuation of blood pressure and angiogenesis factors within the blood circulation during the treatment could be expected to be the index to forecast the efficacy of using anti-angiogenic medicine. CONCLUSIONS： The efficacy of anti-angiogenic therapy alone is short-lasting in most cases,with drug resistance developing within a few months. The knowledge of this resistance and its mechanisms is still evolving,which needs further research and is important for the applications of anti-angiogenic treat ments.