Molecular Mechanisms of Drug Resistance in Single-Step and Multi-Step Drug-Selected Cancer Cells

Abstract

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.