Is resistance useless? Multidrug resistance and collateral sensitivity

被引：232

作者：

Hall, Matthew D. ^{[1
]}

Handley, Misty D. ^{[1
]}

Gottesman, Michael M. ^{[1
]}

机构：

[1] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA

来源：

TRENDS IN PHARMACOLOGICAL SCIENCES | 2009年 / 30卷 / 10期

基金：

美国国家卫生研究院;

关键词：

HAMSTER OVARY CELLS; BREAST-CANCER-CELLS; MAGNETIC-RESONANCE SPECTROSCOPY; MDR1; GENE-EXPRESSION; K562; LEUKEMIC-CELLS; P-GLYCOPROTEIN; CROSS-RESISTANCE; DRUG-RESISTANCE; TUMOR-CELLS; IRON CHELATORS;

D O I：

10.1016/j.tips.2009.07.003

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：546 / 556

页数：11

共 127 条

[41] Relationship between cytotoxic drug response patterns and activity of drug efflux transporters mediating multidrug resistance [J].