Pharmacogenetics of ABC and SLC transporters in metastatic colorectal cancer patients receiving first-line FOLFIRI treatment

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: Membrane transporters are widely recognized as important determinants of drug disposition and response, generating increasing interest on the pharmacological implications of their genetic variations. The aim of this study was to elucidate the predictive/prognostic role of ATP-binding cassette (ABC) and solute carrier (SLC) protein polymorphisms on irinotecan (FOLFIRI regimen) outcome. PATIENTS AND METHODS: A total of 250 White metastatic colorectal cancer patients homogenously treated with a first-line FOLFIRI regimen were genotyped for a panel of variants in five transporter genes. The primary study endpoints were the response rate (partial or complete response), overall survival, and time to progression. Toxicity was considered a secondary endpoint. Irinotecan pharmacokinetic data of 71 patients were used for polymorphism functional analysis. RESULTS: Two variants of the ABCG2 (-15622C>T, rs7699188) gene were found to be predictive (PT, rs7699188) and ABCB1 (rs2032582) polymorphisms were not found to be associated with pharmacokinetic parameters. CONCLUSION: This study showed that ABC/SLC polymorphisms have a crucial contribution toward the FOLFIRI outcome. This could represent a further step toward personalized therapy.

Original languageEnglish
Pages (from-to)549-557
Number of pages9
JournalPharmacogenetics and Genomics
Volume23
Issue number10
DOIs
Publication statusPublished - Oct 2013

Keywords

  • ABC/SLC transporter genetic markers
  • colorectal cancer
  • FOLFIRI
  • genotype/phenotype association
  • irinotecan
  • pharmacogenomics
  • pharmacokinetics
  • response
  • survival
  • UGT1As genetic markers

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)

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