Mansouri A, Henle K J, Nagle W A, Moss A J
John L. McClellan Memorial Veterans Hospital, Little Rock, AR.
SAAS Bull Biochem Biotechnol. 1990 Jan;3:91-6.
Tumors that formerly were uniformly fatal can now be cured by cancer chemotherapy. However, successful anticancer therapy is faced by many obstacles, such as excessive normal tissue toxicity and drug resistance. Tumor drug resistance may be either intrinsic or acquired. The multidrug resistance (MDR) is a unique phenomenon and is characterized by tumor resistance to various structurally unrelated drugs. Known mechanisms for MDR include overexpression of a membrane P-glycoprotein 170 and elevated cellular levels of reducing agents, such as glutathione (GSH). Currently available strategies for overcoming drug resistance include competitive inhibitors of the P-glycoprotein 170, inhibitors of GSH synthesis, and adjuvant therapy with hyperthermia. Development of drug resistance is analogous to a physiological detoxification mechanism and may continue to limit the effectiveness of cancer chemotherapy in the near future.
以前一直都是致命的肿瘤现在可以通过癌症化疗治愈。然而，成功的抗癌治疗面临着许多障碍，比如正常组织毒性过大和耐药性。肿瘤耐药性可能是内在的，也可能是后天获得的。多药耐药（MDR）是一种独特的现象，其特征是肿瘤对各种结构不相关的药物产生抗性。已知的多药耐药机制包括膜P-糖蛋白170的过度表达以及细胞内还原剂（如谷胱甘肽（GSH））水平的升高。目前可用的克服耐药性的策略包括P-糖蛋白170的竞争性抑制剂、GSH合成抑制剂以及热疗辅助治疗。耐药性的产生类似于一种生理解毒机制，在不久的将来可能会继续限制癌症化疗的效果。
