Many solute carrier transporters that interact with
anticancer agents and contribute to their pharmacokinetics have been shown to be differentially upregulated in
cancer cells as a result of adaptive response to altered nutritional requirements. This review focuses on pathophysiological function of
membrane transporters responsible for the influx of physiological substances including
oligopeptides,
amino acids, and organic
cations and
anions, and summarizes the recent knowledge regarding mechanisms in their gene expressions. Broad substrate specificity of enhanced
oligopeptide H(+) /
peptide cotransporter 1 activity in
cancer cells is useful for
tumor tissue-specific delivery of chemotherapeutic agents and positron emission tomography diagnostic probes.
Amino acid transporters such as LAT1 and ASCT2 are upregulated in human
cancer cells and are thought to stimulate
tumor growth by regulating
mammalian target of rapamycin through nutrient pathway. Especially, LAT1 could be a molecular target to deprive
cancer cells of
amino acids in combination with
aminopeptidase inhibitors. As organic
anion transporting
polypeptides carry
estrone-3-sulfate that is intracellularly hydrolyzed to
estrone, their overexpression may provide a pharmacological merit to treat
hormone-responsive
breast tumors. Therefore, it is important to understand the pathophysiological significance and gene expression in
cancer to develop new rationales for
drug delivery and pharmacological interventions for
chemotherapy.