Pharmacogenomics of genes involved in antifolate drug response and toxicity in osteosarcoma

Claudia Maria Hattinger, Elisa Tavanti, Marilù Fanelli, Serena Vella, Piero Picci, Massimo Serra

Research output: Contribution to journalReview article

Abstract

Introduction: Antifolates are structural analogs of folates, which have been used as antitumor drugs for more than 60 years. The antifolate drug most commonly used for treating human tumors is methotrexate (MTX), which is utilized widely in first-line treatment protocols of high-grade osteosarcoma (HGOS). In addition to MTX, two other antifolates, trimetrexate and pemetrexed, have been tested in clinical settings for second-line treatment of recurrent HGOS with patients unfortunately showing modest activity. Areas covered: There is clinical evidence which suggsest that, like other chemotherapeutic agents, not all HGOS patients are equally responsive to antifolates and do not have the same susceptibility to experience adverse drug-related toxicities. Here, we summarize the pharmacogenomic information reported so far for genes involved in antifolate metabolism and transport and in MTX-related toxicity in HGOS patients. Expert opinion: Identification and validation of genetic biomarkers that significantly impact clinical antifolate treatment response and related toxicity may provide the basis for a future treatment modulation based on the pharmacogenetic and pharmacogenomic features of HGOS patients.

Original languageEnglish
Pages (from-to)245-257
Number of pages13
JournalExpert Opinion on Drug Metabolism and Toxicology
Volume13
Issue number3
DOIs
Publication statusPublished - Mar 4 2017

Keywords

  • methotrexate
  • Osteosarcoma
  • pharmacogenetic
  • pharmacogenomic
  • toxicity
  • treatment response

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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