Role of Multidrug Resistance Proteins (MRP) in Resistance to Antifolates and Folate Homeostasis
2002
Cellular folate homeostasis is essential to allow continuous use of reduced folate cofactors for a variety of biosynthetic processes including purine and pyrimidine biosynthesis, mitochondrial protein synthesis and amino acid biosynthesis. Beyond this, there is accumulating evidence that the antiproliferative and/or anti-inflammatory effects of methotrexate (MTX) or second/third generation of folate antagonists is dependent on the patients cellular folate status. High intra-/extracellular folate levels may abrogate the efficacy of folate antagonists, while low intra-/extracellular folate levels may play a role in determining toxic effects (1,2).
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