Holte H
Avdeling for patologi, Institutt for Kreftforskning, Det Norske Radiumhospital, Oslo.
Tidsskr Nor Laegeforen. 1991 Aug 20;111(19):2423-7.
Despite considerable efforts, rather limited progress has been achieved in the treatment of disseminated cancer with chemotherapeutic agents during the last decade. Most tumours, especially those of epithelial origin, are more or less resistant to cytostatics right from initiation of therapy. Other tumours, on the other hand, like leukemias and lymphomas, are highly responsive initially but may become resistant during the course of therapy (secondary resistance). This type of resistance is due to random mutations in the malignant cells. Several mechanisms of cellular resistance have been described, the most important being characterized by simultaneous resistance to several unrelated chemotherapeutic agents (pleiotropic drug resistance or multidrug resistance). This mechanism is due to a membrane-associated efflux pump which transports the cytostatic agents out of the cells. The clinical importance of multidrug resistance and the possibility of inhibiting the function of the pump by pharmacological agents are currently being examined.
尽管付出了巨大努力，但在过去十年中，使用化疗药物治疗播散性癌症取得的进展相当有限。大多数肿瘤，尤其是上皮起源的肿瘤，从治疗开始就或多或少对细胞抑制剂有抗性。另一方面，其他肿瘤，如白血病和淋巴瘤，最初反应高度敏感，但在治疗过程中可能会产生抗性（继发性抗性）。这种抗性类型是由于恶性细胞中的随机突变。已经描述了几种细胞抗性机制，其中最重要的特征是对几种不相关化疗药物同时具有抗性（多向性耐药或多药耐药）。这种机制是由于一种与膜相关的外排泵，它将细胞抑制剂转运出细胞。目前正在研究多药耐药的临床重要性以及通过药物抑制泵功能的可能性。
