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Methods Mol Biol. 2010;596:77-93. doi: 10.1007/978-1-60761-416-6_5.

Molecular mechanisms of drug resistance in single-step and multi-step drug-selected cancer cells.

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Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.


Multidrug resistance (MDR) remains one of the key determinants in chemotherapeutic success of cancer patients. Often, acquired resistance is mediated by the overexpression of ATP-binding cassette (ABC) drug transporters. To study the mechanisms involved in the MDR phenotype, investigators have generated a variety of in vitro cell culture models using both multi-step and single-step drug selections. Sublines produced from multi-step selections have led to the discovery of several crucial drug transporters including ABCB1, ABCC1, and ABCG2. Additionally, a number of mechanisms causing gene overexpression have been elucidated. To more closely mimic in vivo conditions, investigators have also established MDR sublines with single-step drug selections. Here, we examine some of the multi-step and single-step selected cell lines generated to elucidate the mechanisms involved in the development of MDR in cancer cells.

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