Metastasis and Drug Resistance
Metastasis and Drug Resistance
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DOI：
10.1007/978-0-387-89445-4_2
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发表时间：
2009-01-01
期刊：
影响因子：
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通讯作者：
Fidler, Isaiah J.
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文献类型：
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作者：
Fan, Dominic;Kim, Sun-Jin;Fidler, Isaiah J.
化疗产生的多药耐药（MDR）表型是治疗转移性癌症患者的一个主要问题。心血管药物维拉帕米可以与 P-糖蛋白结合并逆转 MDR 的发现引发了对各种化合物和药理学修饰剂模式逆转 MDR 的认真研究工作。这些包括主要的钙通道阻滞剂，如贝普地尔、地尔硫卓、非洛地平、伊拉地平、尼卡地平、硝苯地平和尼莫地平、维拉帕米和类似物；钙调蛋白拮抗剂；抗生素及类似物；吲哚生物碱；环孢菌素及其类似物；激素和抗激素；药用乳化表面活性剂；脂质体封装；大多数研究针对的是 MDR 机制之一：P-糖蛋白。这些研究在体外和有限的体内动物条件下取得了成功；临床试验的相关性仍然缺乏。因此，尚无有效的逆转多药耐药的化疗方案。本章的目的是回顾过去和当前逆转 MDR 的实验，特别是相关癌症转移模型中针对耐药性的重要性。
Multidrug resistance (MDR) phenotype emerging from chemotherapy is a major problem in managing patients with metastatic cancers. The discovery that a cardiovascular drug, verapamil, can bind to P-glycoprotein and reverse MDR initiated serious research efforts in MDR-reversal by various compounds and modes of pharmacological modifiers. Those include major calcium channel blockers such as bepridil, diltiazem, felodipine, isradipine, nicardipine, nifedipine and nimodipine, verapamil and analogs; calmodulin antagonists; antibiotics and analogs; indole alkaloids; cyclosporins and analogs; hormones and antihormones; pharmaceutical emulsifying surfactants; liposomal encapsulation; etc. The majority of the studies targeted one of the MDR mechanisms, P-glycoprotein. These studies have been successful under in vitro and limited in vivo animal conditions; the correlations for clinical trails are still lacking. Therefore, an effective MDR-reversing chemotherapy is not available. It is the purpose of this chapter to review the past and current experimental reversal of MDR and, in particular, the importance in targeting drug resistance in relevant cancer metastasis models.