Methotrexate and Pralatrexate.

Gary S Wood, Jianqiang Wu

Journal: Dermatologic clinics 2016;33(4):747-55

PMID: 26433846

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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.

Address: Department of Dermatology, University of Wisconsin and VA Medical Center, 7th Floor, One South Park, Madison, WI 53715, USA. Electronic address: [email protected].; Department of Dermatology, University of Wisconsin and VA Medical Center, 7th Floor, One South Park, Madison, WI 53715, USA.

DOI: 10.1016/j.det.2015.05.009

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MeSH Terms: Aminopterin, Antimetabolites, Antineoplastic, Apoptosis, DNA Methylation, Epigenesis, Genetic, Folic Acid Antagonists, Humans, Lymphoma, T-Cell, Cutaneous, Methotrexate, S Phase, Skin Neoplasms