The relationship between UGT1A1 gene polymorphism and the metabolism and safety of irinotecan and its liposomes
WANG Jun-long
YU Li-jie
WANG Lei
TIAN Ru
LI Mei
QIU Yun-liang
CUI Yi-min
Abstract：Irinotecan is one of the topoisomerase I inhibitors widely used in various cancer treatments,such as colorectal cancer,lung cancer,and stomach cancer;however,its efficacy and safety are affected by individual genetic differences.Treatment with irinotecan is frequently complicated by severe adverse events(AEs)such as febrile neutropenia and diarrhea.Irinotecan is a pro-drug,which undergoes the conversion in the body into its active metabolite 7-ethyl-10-hydroxy-camptothecin(SN-38).SN-38 is metabolized by UDP glucuronosyltransferase 1A1(UGT1A1)and becomes inactive form.When the gene encoding UGT1A1 mutates and UGT1A1 activity decreases,SN-38 accumulates in the body,which is closely related to the metabolism and toxicity of Irinotecan.UGT1A1 has multiple mutation sites,among which the genetic diversity of UGT1A1∗28 and UGT1A1∗6 has a more significant impact on the toxicity of irinotecan.This article reviews how UGT1A1 gene polymorphism affects the metabolism,efficacy,and safety of irinotecan and its liposomes(such as Onivyde),which will guide the personalized treatment.
Keywords：irinotecanuridine diphosphate-glucuronosyl transferase 1A1genetic polymorphismmetabolismtoxicity
Publication Date：2025-06-15
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：5( 1228-1232 )