The great multidrug-resistance paradox
The great multidrug-resistance paradox
复制标题
DOI：
10.1021/cb600215q
复制
发表时间：
2006-01-01
影响因子：
4
通讯作者：
Rosania, Gus R.
中科院分区：
文献类型：
--
作者：
Chen, Vivien Y.;Rosania, Gus R.
人们对肿瘤细胞多药耐药机制的研究主要集中在跨膜药物转运蛋白及其将药物分子从胞浆输送到细胞外介质的能力。然而，耐药细胞的细胞内药物浓度往往很高，因此不能解释质膜上的药物泵是如何产生多药耐药的。最近的工作表明，细胞质细胞器中的药物隔离如何解释这些矛盾的结果，以及如何利用细胞药代动力学来针对特定细胞类型的小分子活性。
Much of the attention devoted to the elucidation of multidrug-resistance mechanisms in tumor cells has focused on transmembrane drug transporters and their ability to pump drug molecules from the cytosol to the extracellular medium. However, intracellular drug concentrations often remain high in drug-resistant cells and therefore do not explain how drug pumping at the plasma membrane confers multidrug resistance. Recent work indicates how drug sequestration in cytoplasmic organelles can account for these paradoxical results and how cellular pharmacokinetics may be exploited to target the activity of small molecules to specific cell types.