Pathway Methotrexate Pathway (Brain Cell), Pharmacokinetics

Representation of transport and exchange of methotrexate in the brain.
Methotrexate Pathway (Brain Cell), Pharmacokinetics
slc22a8 slc22a6 abcb1 abcc1 abcc4 slc22a8 abcc4 abcb1 abcg2 slco1a2 slc22a8 mtx mtx mtx mtx
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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.

Authors: Torben S. Mikkelsen, Caroline F. Thorn and Jun J. Yang.
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).
Therapeutic Categories:
  • Anticancer agents

Entities in the Pathway

Genes (7)

Drugs/Drug Classes (1)

Relationships in the Pathway

Arrow FromArrow ToControllersPMID
methotrexate methotrexate ABCB1
methotrexate methotrexate SLC22A6, SLC22A8 12011098, 7388786
methotrexate methotrexate ABCB1, ABCC4, ABCG2, SLC22A8 16146333
methotrexate methotrexate ABCC1, ABCC4 11139374
methotrexate methotrexate SLCO1A2 16702441
SLC22A8 methotrexate SLC22A8

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