肿瘤抗血管生成治疗耐药机制  

Drug resistance mechanism of anti-angiogenesis therapy in tumor

作　　者：闫旭 郭影 孙冬琳[1,2] 吴楠 金焰[1,2] Xu Yan;Ying Guo;Donglin Sun;Nan Wu;Yan Jin(Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China(Harbin Medical University),Harbin 150081,China;Ministry of Education and Laboratory of Medical Genetics,Harbin Medical University,Harbin 150081,China)

机构地区：[1]中国遗传资源保护与疾病防控教育部重点实验室(哈尔滨医科大学),哈尔滨150081 [2]哈尔滨医科大学医学遗传学研究室,哈尔滨150081

出　　处：《遗传》2024年第11期911-919,共9页Hereditas（Beijing)

基　　金：国家自然科学基金面上项目(编号:82172353);黑龙江省省属科研院所科研业务费项目(编号:CZKYF2021-2-B012);中国博士后科学基金特别资助(编号:2020T130159);黑龙江省博士后特别资助(编号:LBH-TZ2020);黑龙江省自然科学基金项目(编号:YQ2022H004);黑龙江省头雁创新团队项目资助。

摘　　要：血管生成指的是通过内皮细胞的迁移、增殖和分化,从现有血管网络中形成新的血管网络的过程。这一过程对于实体肿瘤的生长和扩散至关重要,尤其是在肿瘤体积超过2 mm^(3)之后,新生的血管网络为肿瘤提供了至关重要的氧气、营养及生长因子。抗血管生成已经成为临床常用靶向治疗肿瘤的方案之一。首个抗血管生成药物贝伐单抗已广泛应用于多种实体肿瘤治疗,但由于获得性耐药现象,疗效仅能维持1~2年。即使血管内皮细胞的基因组相对稳定,不易产生耐药性,但临床实践中仍观察到多种类型的耐药现象,这表明抗血管生成治疗的耐药问题仍然是一个具有挑战性的研究领域。本文主要综述了肿瘤抗血管生成治疗耐药机制的最新进展,并探讨了抗肿瘤血管生成治疗的新前景,以期为临床实践提供有力的理论支持和指导。Angiogenesis refers to the process of forming a new network of blood vessels from existing ones through the migration,proliferation,and differentiation of endothelial cells.This process is crucial for the growth and spread of solid tumors,particularly once the tumor volume exceeds 2 mm^(3),as the newly formed vascular network provides essential oxygen,nutrients,and growth factors to the tumor.Anti-angiogenesis therapy has become one of the commonly used targeted treatments for cancer in clinical practice.Bevacizumab,the first anti-angiogenesis drug,has been widely applied in the treatment of various solid tumors.However,due to acquired resistance,its efficacy is typically sustained for only 1 to 2 years.Despite the relative genomic stability of endothelial cells,which makes resistance less likely,various types of resistance phenomena have been observed in clinical practice,indicating that resistance to anti-angiogenic therapy remains a challenging research area.This review focuses on the latest advances in the mechanisms of resistance to anti-angiogenic therapy in tumors and explores new prospects for anti-tumor angiogenesis treatment,in order to provide strong theoretical support and guidance for clinical practice.

关 键 词：肿瘤耐药 抗血管生成 血管共选择 血管拟态 血管套叠 

分 类 号：R730.5[医药卫生—肿瘤]