Impact of Breast Cancer Resistance Protein on Cancer Treatment Outcomes
Impact of Breast Cancer Resistance Protein on Cancer Treatment Outcomes
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DOI：
10.1007/978-1-60761-416-6_12
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发表时间：
2010-01-01
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影响因子：
--
通讯作者：
Nakanishi, Takeo
中科院分区：
文献类型：
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作者：
Ross, Douglas D.;Nakanishi, Takeo
乳腺癌耐药蛋白（BCRP/ABCG 2）是在具有ATP依赖性转运的耐药表型的多药耐药乳腺癌细胞中发现的。这种ABC转运蛋白的功能（至少部分）是生物体的外源性保护机制：在肠道和胆道中，它阻止吸收并增强潜在有毒物质的消除。作为胎盘屏障，它保护胎儿;类似地，它作为血脑和血睾丸屏障的组成部分; BCRP在干细胞中表达，可以保护它们免受潜在有害物质的侵害。因此，BCRP可能通过以下方式影响癌症结局：（a）内源性BCRP影响抗癌药物的吸收、分布、代谢和消除;（B）癌细胞中的BCRP表达可能通过抗癌药物的主动外排直接导致耐药;（c）癌细胞中的BCRP表达可能是代谢和信号传导途径活性的表现，这些途径赋予多种耐药机制，自我更新（干性）和侵袭性（攻击性）--即对癌症预后不良。本章简要介绍了白血病、淋巴瘤和各种实体瘤中BCRP表达与临床结局相关的转化临床研究。数据显示，BCRP的表达与P-糖蛋白/ABCB 1一样，与多种人类癌症的不良结局相关。这种不良预后效应是否是由于抗癌药物的BCRP外排直接导致癌细胞产生耐药性，或者BCRP表达是否（以及Pgp表达-这些转运蛋白的共表达在低风险癌症中是常见的）作为信号传导途径活性的指标，所述信号传导途径增强癌症细胞增殖、转移、基因组不稳定性，增强耐药性，和对抗程序性细胞死亡的机制尚不清楚。
Breast cancer resistance protein (BCRP/ABCG2) was discovered in multidrug resistant breast cancer cells having an ATP-dependent transport-based resistance phenotype. This ABC transporter functions (at least in part) as a xenobiotic protective mechanism for the organism: in the gut and biliary tract, it prevents absorption and enhances elimination of potentially toxic substances. As a placental barrier, it protects the fetus; similarly, it serves as a component of blood-brain and blood-testis barrier; BCRP is expressed in stern cells and may protect them from potentially harmful agents. Therefore, BCRP could influence cancer outcomes by (a) endogenous BCRP affecting the absorption, distribution, metabolism, and elimination of anticancer drugs; (b) BCRP expression in cancer cells may directly cause resistance by active efflux of anticancer drugs; (c) BCRP expression in cancer cells could be a manifestation of the activity of metabolic and signaling pathways that impart multiple mechanisms of drug resistance, self-renewal (stemness), and invasiveness (aggressiveness) - i.e. impart a poor prognosis - to cancers. This chapter presents a synopsis of translational clinical studies relating BCRP expression in leukemias, lymphomas, and a variety of solid tumors with clinical outcome. Data are emerging that expression of BCRP, like P-glycoprotein/ABCB1, is associated with adverse Outcomes in a variety of human cancers. Whether this adverse prognostic effect results from resistance imparted to the cancer cells as the direct result of BCRP efflux of anticancer drugs, or whether BCRP expression (and also Pgp expression - coexpression of these transporters is common among poor risk cancers) serves as indicators of the activity of signaling pathways that enhance cancer cellular proliferation, metastases, genomic instability, enhance drug resistance, and oppose programmed cell death mechanisms is yet unknown.