期刊
JOURNAL OF CHEMOTHERAPY
卷 20, 期 2, 页码 158-165出版社
TAYLOR & FRANCIS LTD
DOI: 10.1179/joc.2008.20.2.158
关键词
CRC : colorectal cancer; SN38 : 7-ethyl-10-hydroxycamptothecin; hCE : human carboxylesterases; APC : 7-ethyl-10-[4-N-(5-amino pentanoic acid)-1-piperidino]-carbonyloxycamptothecin; NPC : 7-ethyl-10-[4-(1-piperidino)-1-amino]-carbonyloxycamptothecin; UGT : UDP-glucuronosyltransferase; SNP : Single Nucleotide Polymorphism; LD : Linkage Disequilibrium
Irinotecan is a drug commonly used for the treatment of cancer patients, both as a single agent or in combination therapy. Neutropenia and diarrhea are the dose-limiting toxicities. Genetic variations of proteins involved in irinotecan metabolism and transport have been considered in the development of irinotecan toxicity. In particular, polymorphisms affecting UDP-glucuronosyltransferase isoform 1A1 (UGT1A1) expression or activity are being investigated. Among these, UGT1A1*28 has been considered as the major predictive pharmacogenetic marker for severe hematological toxicity (neutropenia). However, translation to clinical practice of UGT1A1*28 testing as a predictive marker of adverse effects needs to be further investigated and the available data are not conclusive in defining a precise genotype-based dosage. Further prospective studies are required to reach a personalization of chemotherapy with irinotecan.
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