Mechanisms of Multidrug Resistance in Cancer
Mechanisms of Multidrug Resistance in Cancer
复制标题
DOI：
10.1007/978-1-60761-416-6_4
复制
发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Gottesman, Michael M.
中科院分区：
文献类型：
--
作者：
Gillet, Jean-Pierre;Gottesman, Michael M.
对化疗的多药耐药性（MDR）的发展仍然是癌症治疗的主要挑战。每种有效的抗癌药物都存在耐药性，耐药性可以通过多种机制产生，包括药物摄取减少、药物外流增加、解毒系统激活、DNA修复机制激活、药物诱导的细胞凋亡逃避等。在本章的第一部分，我们简要总结了目前对导致MDR的个体细胞机制的了解，特别强调了油ATP结合盒转运蛋白，这也许是本教科书的主题。尽管已经开展了大量工作来表征体外 MDR 机制，但将这些知识转化为临床尚未取得成功。因此，识别对体内 MDR 发展至关重要的基因和机制，并建立分析临床样本的可靠方法，有助于预测耐药性的发展，并找到旨在规避耐药性的治疗方法。因此，我们对在理解这一复杂现象方面取得重大进展所需的转化研究的想法将在第三部分讨论。结论图中总结了癌细胞对化疗的多效性反应。
The development of multidrug resistance (MDR) to chemotherapy remains a major challenge in the treatment of cancer. Resistance exists against every effective anticancer drug and can develop by numerous mechanisms including decreased drug uptake, increased drug efflux, activation of detoxifying systems, activation of DNA repair mechanisms, evasion of drug-induced apoptosis, etc. In the first part of this chapter, we briefly summarize the Current knowledge on individual cellular mechanisms responsible for MDR, with a special emphasis oil ATP-binding cassette transporters, perhaps the main theme of this textbook. Although extensive work has been done to characterize MDR mechanisms in vitro, the translation of this knowledge to the clinic has not been crowned with Success. Therefore, identifying genes and mechanisms critical to the development of MDR in vivo and establishing a reliable method for analyzing clinical samples could help to predict the development of resistance and lead to treatments designed to circumvent it. Our thoughts about translational research needed to achieve significant progress in the understanding of this complex phenomenon are therefore discussed in a third section. The pleotropic response of cancer cells to chemotherapy is summarized in a concluding diagram.