title: Methotrexate and Pralatrexate.
abstract: This article reviews methotrexate and the more potent, related compound, pralatrexate, for the treatment of cutaneous T-cell lymphomas, including mycosis fungoides, Sézary syndrome, and CD30+ lymphoproliferative disorders. Although these folate antagonists are traditionally viewed as antiproliferative cell cycle inhibitors, it is recognized that they inhibit DNA methylation, providing a rationale for their use as epigenetic regulators and cell proliferation inhibitors. The underlying mechanisms are outlined, key supporting data presented, followed by brief mention of recent mathematical modeling supporting the general superiority of combination therapy. Several novel examples involving folate antagonists are proposed.
authors.affiliation: Department of Dermatology, University of Wisconsin and VA Medical Center, 7th Floor, One South Park, Madison, WI 53715, USA. Electronic address: gwood@dermatology.wisc.edu.
authors.forename: Gary S
authors.initials: GS
authors.lastname: Wood
authors.affiliation: Department of Dermatology, University of Wisconsin and VA Medical Center, 7th Floor, One South Park, Madison, WI 53715, USA.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Wu
mesh_terms: D000630:Aminopterin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects; D005493:Folic Acid Antagonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy*; D008727:Methotrexate / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016196:S Phase / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy*
chemical_list: C418863:10-propargyl-10-deazaaminopterin; D000964:Antimetabolites, Antineoplastic; D005493:Folic Acid Antagonists; D000630:Aminopterin; D008727:Methotrexate
keywords: Apoptosis; Dihydrofolate reductase; Folate; Folic acid; Methotrexate; Pralatrexate; Purine synthesis; S phase