Impairment of methotrexate transport is common in osteosarcoma tumor samples.

Article Details

Citation

Sowers R, Wenzel BD, Richardson C, Meyers PA, Healey JH, Levy AS, Gorlick R

Impairment of methotrexate transport is common in osteosarcoma tumor samples.

Sarcoma. 2011;2011:834170. doi: 10.1155/2011/834170. Epub 2010 Dec 22.

PubMed ID
21234348 [ View in PubMed
]
Abstract

Osteosarcoma does not respond well to conventional dose methotrexate but does respond to high-dose methotrexate. Previous work has indicated that this resistance may be due to impaired transport of methotrexate across the cell membrane. In this study, the PT430 competitive displacement assay was adapted to evaluate methotrexate transport in 69 high-grade osteosarcoma tumor samples. All samples studied were shown to have relatively impaired methotrexate transport by PT430 assay. Ninety-nine percent of the samples had less than 20% PT430 displacement by methotrexate. Eighty-eight percent exhibited displacement by methotrexate at less than 50% of the displacement by trimetrexate. The high frequency of impaired transport suggests the presence of decreased functionality of the reduced folate carrier protein. The overwhelming presence of impaired transport may explain why methotrexate needs to be given in high doses to be effective in osteosarcoma therapy and suggests that reduced folate carrier-independent antifolates should be explored.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
TrimetrexateDihydrofolate reductaseProteinHumans
Yes
Inhibitor
Details
Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
TrimetrexateFolate transporter 1ProteinHumans
Unknown
Substrate
Details