Ugt1a1 guided cancer therapy: Review of the evidence and considerations for clinical implementation

Ryan S. Nelson, Nathan D. Seligson, Sal Bottiglieri, Estrella Carballido, Alex Del Cueto, Iman Imanirad, Richard Levine, Alexander S. Parker, Sandra M. Swain, Emma M. Tillman, J. Kevin Hicks

Research output: Contribution to journalArticlepeer-review

Abstract

Multi-gene assays often include UGT1A1 and, in certain instances, may report associated toxicity risks for irinotecan, belinostat, pazopanib, and nilotinib. However, guidance for incorporating UGT1A1 results into therapeutic decision-making is mostly lacking for these anticancer drugs. We summarized meta-analyses, genome-wide association studies, clinical trials, drug labels, and guidelines relating to the impact of UGT1A1 polymorphisms on irinotecan, belinostat, pazopanib, or nilotinib toxicities. For irinotecan, UGT1A1*28 was significantly associated with neutropenia and diarrhea, particularly with doses ≥ 180 mg/m2, supporting the use of UGT1A1 to guide irinotecan prescribing. The drug label for belinostat recommends a reduced starting dose of 750 mg/m2 for UGT1A1*28 homozygotes, though published studies supporting this recommendation are sparse. There was a correlation between UGT1A1 polymorphisms and pazopanib-induced hepatotoxicity, though further studies are needed to elucidate the role of UGT1A1-guided pazopanib dose adjust-ments. Limited studies have investigated the association between UGT1A1 polymorphisms and nilotinib-induced hepatotoxicity, with data currently insufficient for UGT1A1-guided nilotinib dose adjustments.

Original languageEnglish (US)
Article number1566
JournalCancers
Volume13
Issue number7
DOIs
StatePublished - Apr 1 2021

Keywords

  • Belinostat
  • Cancer
  • Geno-type
  • Gilbert’s syndrome
  • Irinotecan
  • Nilotinib
  • Pazopanib
  • Pharmacogenetics
  • Precision medicine
  • UGT1A1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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