Resistance mechanisms to methotrexate in tumors Journal Article

  


Authors: Bertino, J. R.; Göker, E.; Gorlick, R.; Li, W. W.; Banerjee, D.
Article Title: Resistance mechanisms to methotrexate in tumors
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.
Keywords: leukemia; gene mutation; review; methotrexate; antimetabolites, antineoplastic; genetic transcription; drug resistance; drug resistance, neoplasm; enzyme activity; sarcoma; tumor suppressor gene; drug mechanism; drug retention; drug uptake; folinic acid; soft tissue sarcoma; rna translation; acute lymphocytic leukemia; dihydrofolate reductase; folic acid antagonists; tetrahydrofolate dehydrogenase; retinoblastoma protein; biological transport; aminopterin; genes, tumor suppressor; trimetrexate; gamma glutamyl hydrolase; polyglutamic acid; humans; human; folylpolyglutamate synthase; folylpolyglutamate synthetase; γ-glutamyl hydrolase
Journal Title: Stem Cells
Volume: 14
Issue: 1
ISSN: 1066-5099
Publisher: AlphaMed Press  
Date Published: 1996-01-01
Start Page: 5
End Page: 9
Language: English
PUBMED: 8820944
PROVIDER: scopus
DOI: 10.1002/stem.140005
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0030054105&partnerID=40&md5=99f46962ffbe356bf680c5b0cda817e8
Notes: Review -- Export Date: 22 November 2017 -- Source: Scopus
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MSK Authors
  1. Weiwei Li
    63 Li
  2. Debabrata Banerjee
    136 Banerjee
  3. Richard G Gorlick
    121 Gorlick
  4. Joseph Bertino
    363 Bertino
  5. Erdem Göker
    24 Goker
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