de Graeff A, Slebos R J, Rodenhuis S
Division of Experimental Therapy, Netherlands Cancer Institute, Amsterdam.
Cancer Chemother Pharmacol. 1988;22(4):325-32. doi: 10.1007/BF00254240.
In view of the important role of cisplatin (CDDP) in cancer chemotherapy, the frequent occurrence of resistance to the drug is a major clinical problem. The main cause for unresponsiveness of a tumor to CDDP is thought to be cellular drug resistance, which may be caused by (1) a decreased uptake of CDDP, (2) an increase in metallothioneins, (3) an increase in glutathione and/or glutathione-S-transferase, (4) increased DNA repair, or (5) increased tolerance to unrepaired lesions in DNA. Several mechanisms may be concomitantly operative. However, almost all data on CDDP resistance are derived from cell lines or experimental animal systems, and it is uncertain whether they are relevant for human tumors. Possible methods for overcoming CDDP resistance in cancer patients include the use of high-dose CDDP or carboplatin or of different formulations of platinum derivatives, the regional administration of CDDP, the inducement of hyperthermia, the depletion of glutathione by buthionine-S-R-sulfoximine (BSO), or the use of platinum analogues. The development of methods to detect and classify CDDP resistance in human tumor samples is urgently required for the development of modalities to overcome resistance.
鉴于顺铂（CDDP）在癌症化疗中的重要作用，该药物耐药性的频繁出现是一个主要的临床问题。肿瘤对CDDP无反应的主要原因被认为是细胞耐药性，其可能由以下因素引起：（1）CDDP摄取减少；（2）金属硫蛋白增加；（3）谷胱甘肽和/或谷胱甘肽-S-转移酶增加；（4）DNA修复增加；或（5）对DNA中未修复损伤的耐受性增加。几种机制可能同时起作用。然而，几乎所有关于CDDP耐药性的数据都来自细胞系或实验动物系统，它们是否与人类肿瘤相关尚不确定。克服癌症患者CDDP耐药性的可能方法包括使用高剂量CDDP或卡铂或不同配方的铂衍生物、CDDP的区域给药、诱导热疗、用丁硫氨酸-S-R-亚砜胺（BSO）消耗谷胱甘肽或使用铂类似物。为了开发克服耐药性的方法，迫切需要开发检测和分类人类肿瘤样本中CDDP耐药性的方法。
