Year: 1996
Type: article
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.
Source: The Oncologist
Authors: J.R. Bertino, E. Göker, R. Gorlick, W.W. Li, D. Banerjee
Institution: Memorial Sloan Kettering Cancer Center
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G2943714584, G4733012208, G8254997467
OpenAlex ID: W4256316672