Abstract
Over the years chemotherapy failure has been a vital research topic as researchers have been striving to discover reasons behind it. The extensive studies carried out on chemotherapeutic agents confirm that resistance to chemotherapy is a major reason for treatment failure. “Resistance to chemotherapy,” however, is a comprehensive phrase that refers to a variety of different mechanisms in which ATP-binding cassette (ABC) mediated efflux dominates. The ABC is one of the largest gene superfamily of transporters among both eukaryotes and prokaryotes; it represents a variety of genes that code for proteins, which perform countless functions, including drug efflux – a natural process that protects cells from foreign chemicals. Up to date, chemotherapy failure due to ABC drug efflux is an active research topic that continuously provides further evidence on multiple drug resistance (MDR), aiding scientists in tackling and overcoming this issue. This review focuses on drug resistance by ABC efflux transporters in human, viral, parasitic, fungal and bacterial cells and highlights the importance of the MDR permeability glycoprotein being the mutual ABC transporter among all studied organisms. Current developments and future directions to overcome this problem are also discussed.
Highlights
Millions of new cases with infectious/malignant diseases are reported every year; many of them may die due to failure of therapy that is mainly attributed to resistance to chemotherapy (Teillant et al, 2015; Crunkhorn, 2016; Saunders and Lon, 2016)
ATP-binding cassette (ABC) Transporter Family and Failure of Chemotherapy of diseases caused by many causative microorganisms including virus, bacteria, fungi, parasites, or malignant diseases (Leekha et al, 2011; Wijdeven et al, 2016)
The role of drug efflux transporters (P-gp) in failure of HIV treatment with atazanavir was demonstrated by Robillard et al (2013) who showed that mdr1a−/−, mdr1b−/−, and Abcg2−/− triple knockout mice accumulate more atazanavir in their brain and testes compared to their wild-type counterparts
Summary
Millions of new cases with infectious/malignant diseases are reported every year; many of them may die due to failure of therapy that is mainly attributed to resistance to chemotherapy (Teillant et al, 2015; Crunkhorn, 2016; Saunders and Lon, 2016). The ABC is the largest protein transporter superfamily present in all organisms This family of genes codes for different proteins (importers and exporters), which translocate a variety of substrates such as sugars, amino acids, ions, peptides, proteins, cholesterol, metabolites and toxins across extra- and intracellular membranes (Linton, 2007; Broehan et al, 2013; Benadiba and Maor, 2016). Efflux of drugs by ABC transporters decreases intracellular drug concentration causing failure of chemotherapy This efflux mechanism is seen in all living cells, prokaryotes and eukaryotes (Holland and Blight, 1999; Sharom, 2008) and will be discussed in depth in each organism
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