ABSTRACT
This chapter discusses the important considerations pertaining to inter-individual UGT1A1 variability in anticancer pharmacology: genetic variation, tissue expression, genetic diseases, drug-drug interactions, drug-disease interactions, and relevant clinical pharmacogenomics implementation guidelines. The Uridine 5’-diphospho-glucuronosyltransferase family of enzymes facilitate the clearance of a wide variety of endo- and xenobiotics, most of which contain electron-rich heteroatoms. A wide variety of tyrosine kinase inhibitors are used to treat a multitude of diseases. Since many of these therapies are potent inhibitors of UGT1A1, caution should be exercised when combining these therapies with UGT1A1 substrates due to possible DDIs. Most gastrointestinal stromal tumors occur in the stomach, although such tumors also occur in the small intestine, rectum, and esophagus. Data published on UGT1A1 present a complex picture of genetic and environmental effects on anticancer therapy. An extremely wide variety of therapeutics interact in some way with UGT1A1, and numerous endogenous molecules and food constituents also interact with the enzyme.
