Expression of drug efflux pumps: The ATP-binding cassette (ABC) superfamily of proteins includes a number of membrane proteins able to transport a wide diversity of substrates. Besides an ability to transport of toxins out of cells, other substrates include amino acids, peptides, sugars, lipids, steroids, bile salts, nucleotides and endogenous metabolites [
10]. These pumps act to protect cells by ejecting a wide variety of toxins. Although in bacteria this toxin might be an antibiotic, in human cancer it is often an anticancer drug. Classical drug resistance is mediated by the
MDR1 (
ABCB1) gene, which encodes a membrane-based xenobiotic pump molecule, known as phenolic glycoprotein (PgP). This pump is relatively promiscuous and ejects drugs from the cell at a rate that may exceed their entry, rendering the cell resistant. One of the more important molecules of the blood-brain barrier, it has been much studied. This in turn led to the discovery of numerous other pumps, and the human genome contains 49 ABC transporter molecules [
10], many of which can pump drugs. Besides MDR1 the best known are multidrug resistance related protein (
MRP1, ABCC1) and breast cancer related protein (
BCRP, ABCG2). Pharmaceutical chemists now design drugs with this mind, so that pump mechanisms are less problematic than they were, though even some TKIs, including gefitinib and erlotinib [
37,
38], are pumped. Metabolite and nucleotide pumps have also been found to be of importance, and genes such as hENT1 have been reported to be important mediators of chemosensitivity in gene expression studies [
13–
15]. Rapid up-regulation of drugs pumps can occur in cancer cells and lead to resistance [
12].