耐药性是否无用？多重耐药性与协同敏感性。
Is resistance useless? Multidrug resistance and collateral sensitivity.
作者信息
Hall Matthew D, Handley Misty D, Gottesman Michael M
机构信息
Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
出版信息
Trends Pharmacol Sci. 2009 Oct;30(10):546-56. doi: 10.1016/j.tips.2009.07.003. Epub 2009 Sep 15.
Abstract
When cancer cells develop resistance to chemotherapeutics, it is frequently conferred by the ATP-dependent efflux pump P-glycoprotein (MDR1, P-gp, ABCB1). P-gp can efflux a wide range of cancer drugs; its expression confers cross-resistance, termed "multidrug resistance" (MDR), to a wide range of drugs. Strategies to overcome this resistance have been actively sought for more than 30 years, yet clinical solutions do not exist. A less understood aspect of MDR is the hypersensitivity of resistant cancer cells to other drugs, a phenomenon known as "collateral sensitivity" (CS). This review highlights the extent of this effect for the first time, and discusses hypotheses (e.g. generation of reactive oxygen species) to account for the underlying generality of this phenomenon, and proposes exploitation of CS as a strategy to improve response to chemotherapy.
摘要
当癌细胞对化疗药物产生耐药性时，通常是由ATP依赖性外排泵P-糖蛋白（MDR1、P-gp、ABCB1）介导的。P-糖蛋白能够外排多种抗癌药物；其表达赋予了对多种药物的交叉耐药性，即所谓的“多药耐药性”（MDR）。30多年来，人们一直在积极寻找克服这种耐药性的策略，但尚未找到临床解决方案。MDR中一个鲜为人知的方面是耐药癌细胞对其他药物的超敏感性，这一现象被称为“旁杀敏感性”（CS）。本综述首次强调了这种效应的程度，讨论了解释这一现象潜在普遍性的假说（如有氧活性氧的产生），并提出将旁杀敏感性作为一种改善化疗反应的策略加以利用。
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