与微管相关的紫杉醇耐药机制。
Mechanisms of Taxol resistance related to microtubules.
作者信息
Orr George A, Verdier-Pinard Pascal, McDaid Hayley, Horwitz Susan Band
机构信息
Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
出版信息
Oncogene. 2003 Oct 20;22(47):7280-95. doi: 10.1038/sj.onc.1206934.
Abstract
Since its approval by the FDA in 1992 for the treatment of ovarian cancer, the use of Taxol has dramatically increased. Although treatment with Taxol has led to improvement in the duration and quality of life for some cancer patients, the majority eventually develop progressive disease after initially responding to Taxol treatment. Drug resistance represents a major obstacle to improving the overall response and survival of cancer patients. This review focuses on mechanisms of Taxol resistance that occur directly at the microtubule, such as mutations, tubulin isotype selection and post-translational modifications, and also at the level of regulatory proteins. A review of tubulin structure, microtubule dynamics, the mechanism of action of Taxol and its binding site on the microtubule are included, so that the reader can evaluate Taxol resistance in context.
摘要
自1992年被美国食品药品监督管理局（FDA）批准用于治疗卵巢癌以来，紫杉醇的使用量大幅增加。尽管紫杉醇治疗使一些癌症患者的生存期和生活质量得到了改善，但大多数患者在最初对紫杉醇治疗有反应后最终会发展为疾病进展。耐药性是提高癌症患者总体反应率和生存率的主要障碍。本综述重点关注直接发生在微管上的紫杉醇耐药机制，如突变、微管蛋白亚型选择和翻译后修饰，以及调节蛋白水平的机制。文中还对微管蛋白结构、微管动力学、紫杉醇的作用机制及其在微管上的结合位点进行了综述，以便读者在整体背景下评估紫杉醇耐药性。
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