Feun L G, Savaraj N, Landy H J
University of Miami Hospital and Clinics, Florida.
J Neurooncol. 1994;20(2):165-76. doi: 10.1007/BF01052726.
Resistance to chemotherapy in brain tumors is complex and may involve multiple mechanisms. For commonly used drugs, such as nitrosoureas and platinum compounds, major mechanisms may involve increaded DNA repair or removal of the drug-DNA adducts. For water soluble nitrosoureas and also for platinum compounds, other mechanisms, such as alteration in drug transport, may be important. Another major mechanism may involve glutathione and glutathione-S-transferase pathways. For vinca alkaloids and epipodophyllotoxins p-glycoprotein mediated MDR appears to be the major feature in drug resistance. In addition, alteration of tubulin and topoisomerase II have been described in resistance to vinca alkaloids and epipodophyllotoxins respectively. Recently, increased multidrug resistance associated protein gene expression has been found in glioma cells and brain tumor samples; its clinical significance requires further investigation.
脑肿瘤对化疗的耐药性很复杂，可能涉及多种机制。对于常用药物，如亚硝基脲类和铂类化合物，主要机制可能包括DNA修复增加或药物-DNA加合物的清除。对于水溶性亚硝基脲类以及铂类化合物，其他机制，如药物转运改变，可能也很重要。另一个主要机制可能涉及谷胱甘肽和谷胱甘肽-S-转移酶途径。对于长春花生物碱和鬼臼毒素，P-糖蛋白介导的多药耐药似乎是耐药性的主要特征。此外，分别在对长春花生物碱和鬼臼毒素的耐药中描述了微管蛋白和拓扑异构酶II的改变。最近，在胶质瘤细胞和脑肿瘤样本中发现多药耐药相关蛋白基因表达增加；其临床意义需要进一步研究。
