Roles of Uridine Diphosphoglucuronosyltransferase 2B Enzymes in Cancer Susceptibility and Treatment: A Review
Abstract
Uridine diphosphate glucuronosyltransferase 2B (UGT2B) enzymes constitute a critical subgroup of phase II metabolizing enzymes that modulate the clearance of steroid hormones, carcinogens, and numerous anticancer agents, thereby influencing cancer susceptibility, progression, and therapeutic outcomes. This review provides a comprehensive synthesis of the genetic, regulatory, and functional roles of UGT2B family members, particularly UGT2B4, UGT2B7, UGT2B10, UGT2B15, UGT2B17, and UGT2B28, in oncogenesis and cancer treatment. We summarize evidence from molecular, epidemiological, pharmacogenetic, and clinical studies demonstrating how UGT2B expression patterns, polymorphisms, copy number variations, epigenetic regulation, and microRNA-mediated control shape intratumoral hormone homeostasis, carcinogen detoxification, and drug resistance across multiple malignancies, including prostate, breast, lung, colorectal, hematological, and hormone-dependent cancers. UGT2B enzymes metabolize several widely used anticancer drugs and active metabolites, thereby affecting pharmacokinetics, efficacy, and toxicity. Understanding the context-specific roles of UGT2B family members offers a compelling opportunity for therapeutic exploitation. In particular, rational combination strategies incorporating UGT2B inhibitors or modulators alongside standard anticancer agents may enhance drug effectiveness without increasing dosage, while simultaneously enabling the dose reduction of the partner agent…
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