肿瘤多药耐药分子机制研究进展

化疗是治疗恶性肿瘤主要方法之一。然而不幸的是,先天或获得性耐药尤其是多药耐药的发生,最终导致化疗失败。因此,深入探讨多药耐药发生的分子机制,寻找可以有效预测肿瘤化疗敏感性的分子标志物以及逆转多药耐药的分子靶点,是提高化疗效果的有效途径。肿瘤多药耐药分子机制错综复杂,本文主要从DNA损伤修复、ABC转运蛋白家族表达和功能异常、肿瘤干细胞、拓扑异构酶活性改变、上皮间质转分化、谷胱甘肽-S-转移酶表达改变、表观遗传学修饰以及缺氧等方面对肿瘤多药耐药分子机制进行阐述。

The Rresearch Progress in Molecular Mechanisms of Multidrug Resistance in Cancer

ABSTRACT: Chemotherapy is the first-line treatment for patients with advanced cancer. However, even though many novel chemotherapeutic drugs are used in clinical practice, chemotherapeutic approaches fail because of intrinsic or acquired drug resistance, particularly multidrug resistance (MDR). Thus, the exact mechanism of multidrug resistance remains to be further studied. Looking for molecular markers can effectively predict the sensitivity of cancer chemotherapy and searching for the molecular targets to reverse multidrug resistance is an effective way to improve the effect of chemotherapy. The molecular mechanism of multidrug resistance in cancer is complex. This article will focus on the mechanisms of multidrug resistance mainly from the following aspects: DNA damage repair, expression and functional abnormalities of the transporter family, cancer stem cells, the changes of the activity of topoisomerase, epithelial-mesenchymal transitions, changes in expression of glutathione -S- transferase, epigenetic modification and hypoxia.