恶性肿瘤pH依赖性生理性耐药及其对策.pdfVIP

384 　　肿瘤2012 年5 月第32 卷第5 期　TUM OR Vol. 32, May 2012 DOI: 10.3781/j .issn.1000-7431.2012 .05.014 Copyright© 2012 by TUM OR 综述 Review · 恶性肿瘤pH依赖性生理性耐药及其对策 李茹恬，钱 晓萍，刘宝瑞 南京大学医学院附属鼓楼医院肿瘤中心暨南京大学临床肿瘤学研究所 南京　2 10008 ， [ 摘要 ]　目前绝大多数的肿瘤耐药机制研究均集中于肿瘤细胞基因和蛋白水平，而对肿瘤组织微环境的关注则相 对较少。恶性实体瘤实际上是一个类似于器官的异质性实体结构，肿瘤组织微环境中的理化因子，例如肿瘤局部 pH 值、血流、压力和氧供等，均会对药物的疗效产生重要的影响。上述现象被定义为 “生理性耐药”，其不同于 信号通路或蛋白表达改变所引起的耐药。本文将重点介绍肿瘤组织局部pH 值变化引起的耐药，即pH 依赖性生理 性耐药 （pH-induced physiological drug resistance ，PIPDR ）的产生及其临床意义。 [ 关键词 ]　抗药性 肿瘤 纳米粒子 质子泵抑制剂 ， ； ； [中图分类号]　R730.53 [文献标志码]　A [文章编号]　1000-7431 (2012) 05-0384-05 The pH-induced physiological drug resistance and the strategies in the treatment of malignant tumors LI Ru-tian, QIAN Xiao-ping, LIU Bao-rui Oncology Center, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Clinical Oncology Institute of Nanjing University, Nanjing 210008, China [A BSTRACT]　 For the present studies in the field of oncology, most of them concentrate on cellular or genetic changes of cancer cells, but few attention is paid on the microenvironment of tumor tissues. Solid tumors are organ-like structures that are heterogeneous and structurally complex. The altered physicochemical factors in the tumor microenvironment play a vital role in the resistance to anticancer drugs, such as pH, blood flow, interstitial pressure and oxygen supply. This phenomenon is defined as “physiological drug resistance”, which is distinct from the “biochemical drug resistance” caused by the altered signaling pathway or expression of proteins. This paper focuses on the drug resistance caused by altered pH value in microenvironment of