Reduced folate carrier: biochemistry and molecular biology of the normal and methotrexate-resistant cell

The cytotoxic drug methotrexate uses the reduced folate carrier for transport into the cell, where it inhibits key enzymes in nucleotide biosynthesis. Resistance to methotrexate can be achieved by altering the genetic code of the reduced folate carrier gene and thus change the structure and function of the protein. Our understanding of RFC structure and function is based on the information gained from studying the uptake of folates and antifolates in living cells and the application of molecular techniques to determine gene expression and genetic mutations. The aim of this essay is to explain the structure and function of the reduced folate carrier, review the molecular biology of the reduced folate carrier gene and the mutations and polymorphisms that can result in methotrexate resistance.