The association of ABC proteins with multidrug resistance in cancer

Abstract

Multidrug resistance (MDR) poses one of the primary challenges for cancer treatment, especially in cases of metastatic disease. Various mechanisms contribute to MDR, including the overexpression of ATP-binding cassette (ABC) proteins. In this context, we reviewed the literature to establish a correlation between the overexpression of ABC proteins and MDR in cancer, considering both in vitro and clinical studies. Initially, we presented an overview of the seven subfamilies of ABC proteins, along with the subcellular localization of each protein. Subsequently, we identified a panel of 20 ABC proteins (ABCA1–3, ABCA7, ABCB1–2, ABCB4–6, ABCC1–5, ABCC10–11, ABCE1, ABCF2, ABCG1, and ABCG2) associated with MDR. We also emphasize the significance of drug sequestration by certain ABC proteins into intracellular compartments. Among the anticancer drugs linked to MDR, 29 were definitively identified as substrates for at least one of the three most crucial ABC transporters: ABCB1, ABCC1, and ABCG2. We further discussed that the most commonly used drugs in standard regimens for mainly breast cancer, lung cancer, and acute lymphoblastic leukemia could be subject to MDR mediated by ABC transporters. Collectively, these insights will aid in conducting new studies aimed at a deeper understanding of the clinical MDR mediated by ABC proteins and in designing more effective pharmacological treatments to enhance the objective response rate in cancer patients.