Wood Gary S, Wu Jianqiang
Department of Dermatology, University of Wisconsin and VA Medical Center, 7th Floor, One South Park, Madison, WI 53715, USA.
Department of Dermatology, University of Wisconsin and VA Medical Center, 7th Floor, One South Park, Madison, WI 53715, USA.
Dermatol Clin. 2015 Oct;33(4):747-55. doi: 10.1016/j.det.2015.05.009. Epub 2015 Aug 1.
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.
本文综述了甲氨蝶呤以及更强效的相关化合物普拉曲沙，用于治疗皮肤T细胞淋巴瘤，包括蕈样肉芽肿、塞扎里综合征和CD30+淋巴增殖性疾病。尽管这些叶酸拮抗剂传统上被视为抗增殖细胞周期抑制剂，但人们认识到它们能抑制DNA甲基化，这为它们作为表观遗传调节剂和细胞增殖抑制剂的使用提供了理论依据。文中概述了潜在机制，呈现了关键的支持数据，随后简要提及了支持联合治疗总体优势的近期数学模型。还提出了几个涉及叶酸拮抗剂的新例子。
