Genomic and Proteomic Insights into ABC Transporter-Mediated Drug Resistance in Cancer

Abstract

ATP-binding cassette (ABC) transporters play a key role in the development of multidrug resistance (MDR) in cancer, as they actively pump chemotherapeutic agents out of tumor cells, thereby limiting drug accumulation and efficacy Of the 48 known human ABC transporters, members such as P-glycoprotein (ABCB1), MRP1 (ABCC1) and BCRP (ABCG2) are indeed implicated in clinical drug resistance across a variety of malignancies. In this review, we will examine the most recent genomic and proteomic studies on the regulation, expression, and function of ABC transporters in cancer. Genomic studies have identified mutations, polymorphisms, and epigenetic factors that affect transporter activity and expression, thereby contributing to variability in drug response among individuals. Proteomic studies have provided detailed identification of post-translational modifications and protein–protein interactions that can affect transporter stability and trafficking. In addition, multi-omics studies have provided new insights into regulators of ABC transporters and novel therapeutic targets to reverse MDR. A thorough understanding of the molecular complexities of each ABC transporter family member is crucial for establishing predictive biomarkers and developing strategies to overcome drug resistance. This synthesis of genomic and proteomic data supports the need to consider how the variability of different ABC transporters contributes to each individual's resistance, which in turn highlights the need for personalized approaches in cancer therapy to optimize the effects while overcoming the specific mechanisms linked to ABC transporter-mediated drug resistance.