From Bedside to Bench to Bedside to Clinical Practice: An Odyssey with Irinotecan

An odyssey can be defined as “a long wandering and eventful journey” ([1][1]). Traveling together with many collaborators, from a National Cancer Institute–sponsored phase I trial to drug metabolism to genomics, we learned, over more than a decade, the essence of pharmacogenetics, a field with

[1]  Sien‐Sing Yang,et al.  Effects of variant UDP-glucuronosyltransferase 1A1 gene, glucose-6-phosphate dehydrogenase deficiency and thalassemia on cholelithiasis. , 2005, World journal of gastroenterology.

[2]  M. Ratain,et al.  Modulation of irinotecan with cyclosporine: a phase II trial in advanced colorectal cancer , 2005, Cancer Chemotherapy and Pharmacology.

[3]  M. Spillman,et al.  Managing familial risk in genetic testing. , 2004, Genetic testing.

[4]  R. Schilsky,et al.  A phase I trial of pharmacologic modulation of irinotecan with cyclosporine and phenobarbital , 2004, Clinical pharmacology and therapeutics.

[5]  Kazuo Komamura,et al.  UGT1A1 Haplotypes Associated with Reduced Glucuronidation and Increased Serum Bilirubin in Irinotecan‐administered Japanese Patients with Cancer , 2004, Clinical pharmacology and therapeutics.

[6]  Soma Das,et al.  Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  G. Colditz,et al.  The Functional UGT1A1 Promoter Polymorphism Decreases Endometrial Cancer Risk , 2004, Cancer Research.

[8]  R. Schilsky,et al.  UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicity , 2002, The Pharmacogenomics Journal.

[9]  Matthew W. Pennington,et al.  Thirteen UDPglucuronosyltransferase genes are encoded at the human UGT1 gene complex locus. , 2001, Pharmacogenetics.

[10]  D. Spiegelman,et al.  Association of Genetic Polymorphisms in UGT 1 A 1 with Breast Cancer and Plasma Hormone Levels 1 , 2001 .

[11]  H. Saka,et al.  Polymorphisms of UDP-glucuronosyltransferase gene and irinotecan toxicity: a pharmacogenetic analysis. , 2000, Cancer research.

[12]  A. Di Rienzo,et al.  Variability at the uridine diphosphate glucuronosyltransferase 1A1 promoter in human populations and primates. , 1999, Pharmacogenetics.

[13]  A. Di Rienzo,et al.  Phenotype‐genotype correlation of in vitro SN‐38 (active metabolite of irinotecan) and bilirubin glucuronidation in human liver tissue with UGT1A1 promoter polymorphism , 1999, Clinical pharmacology and therapeutics.

[14]  E. Beutler,et al.  Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[15]  M. Ratain,et al.  Genetic predisposition to the metabolism of irinotecan (CPT-11). Role of uridine diphosphate glucuronosyltransferase isoform 1A1 in the glucuronidation of its active metabolite (SN-38) in human liver microsomes. , 1998, The Journal of clinical investigation.

[16]  M. Ratain,et al.  Pharmacokinetic and pharmacodynamic evaluation of the topoisomerase inhibitor irinotecan in cancer patients. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  M. Ratain,et al.  Pharmacokinetic modulation of irinotecan and metabolites by cyclosporin A. , 1996, Cancer research.

[18]  B. Burchell,et al.  Genetic variation in bilirubin UDP-glucuronosyltransferase gene promoter and Gilbert's syndrome , 1996, The Lancet.

[19]  D Lindhout,et al.  The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome. , 1995, The New England journal of medicine.

[20]  M. Ratain,et al.  Metabolic fate of irinotecan in humans: correlation of glucuronidation with diarrhea. , 1994, Cancer research.