Pauly M, Ries F, Dicato M
Laboratoire de Recherche sur le Cancer et les Maladies du Sang, Z.I. Grasbusch, Leudelange, Grand Duchy of Luxembourg.
Pathol Res Pract. 1992 Aug;188(6):804-7. doi: 10.1016/S0344-0338(11)80185-8.
Cellular multidrug resistance, a common side-effect of anticancer chemotherapy frequently leading to failure of the treatment, has been characterized as an acquired resistance to several antimitotic drugs simultaneously. Multidrug resistance could mainly be attributed to the overexpression of the P-170 glycoprotein, considered as a drug-efflux pump encoded by the mdr 1 gene. Overexpression of this protein can be induced either by an accidental amplification or activation or both of the mdr 1 gene. Recent investigations focused on these mechanisms, aiming at a better understanding of the appearance of multidrug resistance during a chemotherapy. P-glycoprotein mediated drug resistance, however, is only one, albeit quite an important detoxification pathway, and some observations revealed genetic interactions with other systems. On the basis of this new knowledge, the development of novel therapeutic strategies to circumvent this clinical side-effect of cancer treatment has already begun.
细胞多药耐药性是抗癌化疗常见的副作用，常导致治疗失败，其特征为同时获得对多种抗有丝分裂药物的耐药性。多药耐药性主要归因于P-170糖蛋白的过表达，该蛋白被认为是由mdr 1基因编码的药物外排泵。该蛋白的过表达可由mdr 1基因的偶然扩增或激活或两者共同作用诱导产生。最近的研究聚焦于这些机制，旨在更好地理解化疗期间多药耐药性的出现。然而，P-糖蛋白介导的耐药性只是一条虽相当重要但的解毒途径，一些观察结果揭示了其与其他系统的基因相互作用。基于这些新知识，旨在规避癌症治疗这一临床副作用的新型治疗策略的研发已经启动。
