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多药耐药(multidrug resistance,MDR)是肿瘤化疗失败最常见而又最难解决的问题。研究MDR机制,开发具有克服MDR作用的新型化疗药物是抗肿瘤药物研究的一个热点领域。肿瘤细胞耐药是一个复杂的、动态的体系,可以发生在细胞膜或细胞质水平,也可发生在细胞解毒系统、DNA修复系统以及药物作用靶点的改变上。该文在总结逆转肿瘤耐药性策略的基础上,对MDR逆转剂、作用于细胞解毒系统以及作用于Bcl-2家族、DNMT和p53等新靶点的小分子药物的研究进展进行综述。
Multidrug resistance (MDR) is the most common and difficult problem of tumor chemotherapy failure. To study the mechanism of MDR and to develop new chemotherapeutic drugs with the function of overcoming MDR is a hot research field of anticancer drugs. Tumor cell resistance is a complex and dynamic system that can occur at the plasma membrane or cytoplasm level, as well as in cell detoxification systems, DNA repair systems, and drug targets. On the basis of summarizing the strategy of reversing tumor drug resistance, this review summarizes the progress of MDR rejuvenating agents, the cell detoxification system and small molecule drugs acting on new targets such as Bcl-2 family, DNMT and p53.