Metabolomics of Drug Resistance in Cancer: The Epigenetic Component

Drug resistance is an important concern in practical medicine, with special relevance in cancer (chemotherapy resistance). Although the molecular mechanisms of drug resistance are still obscure, there is evidence that genetic variation in pathogenic, metabolic, and transporter genes, under the influence of epigenetic events (DNA methylation, chromatin/histone remodeling, miRNA dysregulation), may contribute to drug resistance. Three types of drug efflux pumps, the multidrug resistance gene 1 (MDR1/ABCB1)-encoded P glycoprotein, the multidrug resistance-associated protein (MRP/ABCC1) and breast cancer resistance protein (BCRP/ABCG2) may play an important part in the intrinsic or acquired defense of cells against drugs. Multidrug resistance is often associated with an ATP-dependent decrease in cellular drug accumulation which is attributed to the overexpression of ABC transporter proteins [1,2].