Pharmacogenetics of Irinotecan

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)

Volume 17, 14 Issues, 2017

Download PDF Flyer

Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

This journal supports open access

Aims & ScopeAbstracted/Indexed in

Ranking and Category:
  • 27th of 59 in Chemistry, Medicinal

Submit Abstracts Online Submit Manuscripts Online

Michelle Prudhomme
Institut de Chimie de Clermont-Ferrand
Université Clermont Auvergne

View Full Editorial Board

Subscribe Purchase Articles Order Reprints

Current: 2.722
5 - Year: 2.849

Pharmacogenetics of Irinotecan

Anti-Cancer Agents in Medicinal Chemistry, 3(3): 225-237.

Author(s): G. Toffoli, E. Cecchin, G. Corona and M Boiocchi.

Affiliation: Experimental and Clinical Pharmacology, Unit CRO-National Cancer Institute, 33081 Aviano-PN,Italy.


Pharmacogenetics focuses on intersubjects variation in therapeutic drug effects and toxicity depending on genetic polymorphisms. This is particularly interesting in oncology since anticancer drugs usually have a narrow margin of safety. Irinotecan {7-ethyl-10-[4-(1- piperidino)-1-piperidino]carbonyloxycamptothecin} is used in cancer chemotherapy as a topoisomerase I inhibitor and it is characterised by a sometimes unpredictable severe toxicity. It is mostly intestinal with nausea, vomit and diarrhoea or haematologic with leukothrombocytopenia. Its complex metabolism involves many proteins. Human carboxylesterase isoforms 1 and 2 (hCE1, hCE2) activate irinotecan to its metabolite SN-38 (7-ethyl-10-hydroxycamptothecin), cytochrome P450 isoforms 3A4 and 3A5 (CYP3A4, CYP3A5) mediate the oxidation of the parental compound to irinotecan, uridino-glucuronosil transferase isoform 1A1 (UGT1A1) catalyses glucuronidation of SN-38, the multiresistance protein isoform 2 (MRP2) allows the cellular excretion of the SN-38 glucuronide (SN-38G) and the multi-drug resistance gene (MDR1), encoding for P-glycoprotein, is responsible for the excretion of irinotecan from the cell. Polymorphic structures in the genes encoding for all these proteins have been described. In particular, the UGT1A1*28 allele has been associated with an increased toxicity after irinotecan chemotherapy. Classical parameters used in the clinic, such as body-surface area, have no longer a meaningful correlation with clinical outcome. Hence it emerges the importance of studying the individual genotype to predict the toxicity and efficacy of irinotecan and to individualise therapy. In this review, we summarise the new developments on the study of the pharmacogenetics of irinotecan, stressing its importance in drug cytotoxic effect.


pharmacogenetics, irinotecan, ugt1a1, cyp3a4, hce, mrp2, mdr1 polymorphisms.

Purchase Online Order Reprints Order Eprints Rights and Permissions

Article Details

Volume: 3
Issue Number: 3
First Page: 225
Last Page: 237
Page Count: 13
DOI: 10.2174/1568011033482477
Price: $58
Global Biotechnology Congress 2017Drug Discovery and Therapy World Congress 2017

Related Journals

Related eBooks

Webmaster Contact: Copyright © 2017 Bentham Science