Role of folylpolygutamate synthetase (FPGS) in antifolate chemotherapy; a biochemical and clinical update

Timothy W. Synold, Elizabeth M. Willits, Julio C. Barredo

Research output: Contribution to journalArticle

18 Scopus citations


Even though folate antimetabolites were introduced over forty years ago, they continue to be the backbone of many active chemotherapeutic regimens used by medical and pediatric oncologists. The recognition of polyglutamylation by folylpolyglutamate synthetase (FPGS) as an important metabolic step in the "activation" of classical antifolates and novel drugs aimed at thymidylate synthase (TS) and de novo purine synthesis, has resulted in renewed interest in this class of drugs. In addition, the emergence of secondary neoplasms in patients treated with alkylating agents and topoisomerase inhibitors in contrast to the exceptional safety record of antimetabolites, underscores the need for clinical trials that incorporate new strategies with known active antimetabolites and novel promising agents. In that context, FPGS is an important target for further laboratory and clinical investigations.

Original languageEnglish (US)
Pages (from-to)9-15
Number of pages7
JournalLeukemia and Lymphoma
Issue number1-2
StatePublished - Jan 1 1996



  • Antifolates
  • Chemotherapy
  • FPGS
  • Polyglutamylation

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

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