Resistance mechanisms to methotrexate in tumors

J. R. Bertino, E. Göker, R. Gorlick, W. W. Li, D. Banerjee

Research output: Contribution to journalReview articlepeer-review

37 Scopus citations

Abstract

The mechanisms of intrinsic and acquired resistance to methotrexate (MTX) in human tumors are reviewed herein. In blasts from patients with acute lymphocytic leukemia, resistance mechanisms found are decreased uptake and increased dihydrofolate reductase (DHFR) activity. A major cause of intrinsic resistance to MTX in soft tissue sarcoma cells and in acute myelocytic leukemia appears to be a lack of drug retention, due mainly to low levels of polyglutamylation. A novel association between lack of the retinoblastoma protein and intrinsic MTX resistance has been found. This has been attributed to an increase in DHFR activity, due to an increased rate of transcription of this gene, stimulated by an increase in levels of free E2F, not sequestered by hypophosphorylated retinoblastoma protein.

Original languageEnglish (US)
Pages (from-to)5-9
Number of pages5
JournalSTEM CELLS
Volume14
Issue number1
DOIs
StatePublished - 1996

Keywords

  • Dihydrofolate reductase
  • Drug resistance
  • Folylpolyglutamate synthetase
  • Leukemia
  • Methotrexate
  • Sarcoma
  • Trimetrexate
  • γ-glutamyl hydrolase

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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