MTX-based regimens are widely used for tumors of the central nervous system (CNS) [Article:15987831][Article:10563431]. However, the prognosis for CNS tumors is still very poor likely due to two reasons: low availability of drug at the site of action and intrinsic or acquired resistance the tumor has against the antitumor agents [Article:15987831]. This pathway depicts candidate genes involved in the transport of methotrexate in the brain, showing blood vessel endothelial cells and exchange between the bloodstream, epithelial brain cells in the choroid plexus and cerebrospinal fluid. The transporter genes depicted are polymorphic and several have been studied for their association with methotrexate efficacy and toxicity. For further discussion of methotrexate pharmacogenomics see [Article:21317831] and methotrexate pathway and for details of individual studies see methotrexate variant annotations.
Mikkelsen Torben S, Thorn Caroline F, Yang Jun J, Ulrich Cornelia M, French Deborah, Zaza Gianluigi, Dunnenberger Henry M, Marsh Sharon, McLeod Howard L, Giacomini Kathy, Becker Mara L, Gaedigk Roger, Leeder James Steven, Kager Leo, Relling Mary V, Evans William, Klein Teri E, Altman Russ B . "PharmGKB summary: methotrexate pathway" Pharmacogenetics and genomics (2011).
Entities in the Pathway
Drugs/Drug Classes (1)
Relationships in the Pathway
|Arrow From||Arrow To||Controllers||PMID|
|methotrexate||methotrexate||SLC22A6, SLC22A8||12011098, 7388786|
|methotrexate||methotrexate||ABCB1, ABCC4, ABCG2, SLC22A8||16146333|
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